Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Seminars in Immunopathology
Erschienen in: Seminars in Immunopathology 1/2014

01.01.2014 | Review

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

verfasst von: Petra S. Eisele, Christoph Handschin

Erschienen in: Seminars in Immunopathology | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Skeletal muscle is an organ involved in whole body movement and energy metabolism with the ability to dynamically adapt to different states of (dis-)use. At a molecular level, the peroxisome proliferator-activated receptor γ coactivators 1 (PGC-1s) are important mediators of oxidative metabolism in skeletal muscle and in other organs. Musculoskeletal disorders as well as obesity and its sequelae are associated with PGC-1 dysregulation in muscle with a concomitant local or systemic inflammatory reaction. In this review, we outline the function of PGC-1 coactivators in physiological and pathological conditions as well as the complex interplay of metabolic dysregulation and inflammation in obesity with special focus on skeletal muscle. We further put forward the hypothesis that, in this tissue, oxidative metabolism and inflammatory processes mutually antagonize each other. The nuclear factor κB (NF-κB) pathway thereby plays a key role in linking metabolic and inflammatory programs in muscle cells. We conclude this review with a perspective about the consequences of such a negative crosstalk on the immune system and the possibilities this opens for clinical applications.
Literatur
1.
Thews G, Mutschler E, Vaupel P. (1999) Skelett, Muskulatur und Bindegewebe. In: Anatomie, Physiologie, Pathophysiologie des Menschen, 5th edn. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, pp. 553–603
2.
Lodish H, Berk A, Kaiser CA, Krieger M, Scott MP, Bretscher A, Ploegh H, Matsudaira P (2007) Cellular energetics. In: Molecular cell biology, 6th edn. W.H. Freeman and Company, New York, pp 479–532
3.
Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871PubMedCentralPubMed
4.
Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23:599–622PubMed
5.
Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115:2656–2664PubMedCentralPubMed
6.
Hage Hassan R, Hainault I, Vilquin JT, Samama C, Lasnier F, Ferre P, Foufelle F, Hajduch E (2012) Endoplasmic reticulum stress does not mediate palmitate-induced insulin resistance in mouse and human muscle cells. Diabetologia 55:204–214PubMed
7.
Rieusset J, Chauvin MA, Durand A, Bravard A, Laugerette F, Michalski MC, Vidal H (2012) Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance. Biochem Biophys Res Commun 417:439–445PubMed
8.
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839PubMed
9.
Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876PubMedCentralPubMed
10.
Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM (2003) Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 113:159–170PubMed
11.
Oberkofler H, Schraml E, Krempler F, Patsch W (2003) Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha. Biochem J 371:89–96PubMed
12.
Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (2004) Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev 18:157–169PubMed
13.
Savkur RS, Bramlett KS, Stayrook KR, Nagpal S, Burris TP (2005) Coactivation of the human vitamin D receptor by the peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Mol Pharmacol 68:511–517PubMed
14.
Shiraki T, Sakai N, Kanaya E, Jingami H (2003) Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha, a possible link between xenobiotic response and nutritional state. J Biol Chem 278:11344–11350PubMed
15.
Bhalla S, Ozalp C, Fang S, Xiang L, Kemper JK (2004) Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha, functional implications in hepatic cholesterol and glucose metabolism. J Biol Chem 279:45139–45147PubMed
16.
Tcherepanova I, Puigserver P, Norris JD, Spiegelman BM, McDonnell DP (2000) Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1. J Biol Chem 275:16302–16308PubMed
17.
Huss JM, Kopp RP, Kelly DP (2002) Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 277:40265–40274PubMed
18.
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138PubMed
19.
Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan M, Gonzalez FJ, Spiegelman BM (2003) Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci U S A 100:4012–4017PubMedCentralPubMed
20.
Delerive P, Wu Y, Burris TP, Chin WW, Suen CS (2002) PGC-1 functions as a transcriptional coactivator for the retinoid X receptors. J Biol Chem 277:3913–3917PubMed
21.
Knutti D, Kaul A, Kralli A (2000) A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen. Mol Cell Biol 20:2411–2422PubMedCentralPubMed
22.
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423:550–555PubMed
23.
Olmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, Monsalve M (2009) Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes. J Biol Chem 284:14476–14484PubMed
24.
Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124PubMed
25.
Moore ML, Park EA, McMillin JB (2003) Upstream stimulatory factor represses the induction of carnitine palmitoyltransferase-Ibeta expression by PGC-1. J Biol Chem 278:17263–17268PubMed
26.
Michael LF, Wu Z, Cheatham RB, Puigserver P, Adelmant G, Lehman JJ, Kelly DP, Spiegelman BM (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci U S A 98:3820–3825PubMedCentralPubMed
27.
Lin J, Puigserver P, Donovan J, Tarr P, Spiegelman BM (2002) Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 277:1645–1648PubMed
28.
Kressler D, Schreiber SN, Knutti D, Kralli A (2002) The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha. J Biol Chem 277:13918–13925PubMed
29.
Kamei Y, Ohizumi H, Fujitani Y, Nemoto T, Tanaka T, Takahashi N, Kawada T, Miyoshi M, Ezaki O, Kakizuka A (2003) PPAR{gamma} coactivator 1{beta}/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc Natl Acad Sci U S A 100:12378–12383PubMedCentralPubMed
30.
Hentschke M, Susens U, Borgmeyer U (2002) PGC-1 and PERC, coactivators of the estrogen receptor-related receptor gamma. Biochem Biophys Res Commun 299:872–879PubMed
31.
Lin J, Yang R, Tarr PT, Wu PH, Handschin C, Li S, Yang W, Pei L, Uldry M, Tontonoz P, Newgard CB, Spiegelman BM (2005) Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell 120:261–273PubMed
32.
Oberkofler H, Hafner M, Felder T, Krempler F, Patsch W (2009) Transcriptional co-activator peroxisome proliferator-activated receptor (PPAR)gamma co-activator-1beta is involved in the regulation of glucose-stimulated insulin secretion in INS-1E cells. J Mol Med 87:299–306PubMed
33.
Wolfrum C, Stoffel M (2006) Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. Cell Metab 3:99–110PubMed
34.
Mirebeau-Prunier D, Le Pennec S, Jacques C, Gueguen N, Poirier J, Malthiery Y, Savagner F (2010) Estrogen-related receptor alpha and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria. FEBS J 277:713–725PubMed
35.
Andersson U, Scarpulla RC (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol 21:3738–3749PubMedCentralPubMed
36.
Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (1999) Activation of PPARgamma coactivator-1 through transcription factor docking. Science 286:1368–1371PubMed
37.
Li S, Liu C, Li N, Hao T, Han T, Hill DE, Vidal M, Lin JD (2008) Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab 8:105–117PubMedCentralPubMed
38.
Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (2003) Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell 12:1137–1149PubMed
39.
Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E (2002) Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP. J Biol Chem 277:49761–49766PubMed
40.
Xie YB, Park JH, Kim DK, Hwang JH, Oh S, Park SB, Shong M, Lee IK, Choi HS (2009) Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation. J Biol Chem 284:28762–28774PubMed
41.
Park YY, Ahn SW, Kim HJ, Kim JM, Lee IK, Kang H, Choi HS (2005) An autoregulatory loop controlling orphan nuclear receptor DAX-1 gene expression by orphan nuclear receptor ERRgamma. Nucleic Acids Res 33:6756–6768PubMedCentralPubMed
42.
Nedumaran B, Hong S, Xie YB, Kim YH, Seo WY, Lee MW, Lee CH, Koo SH, Choi HS (2009) DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression. J Biol Chem 284:27511–27523PubMed
43.
Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman BM (2000) Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell 6:307–316PubMed
44.
Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O'Rahilly S, Montague C, Vidal-Puig AJ (2003) Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem J 373:155–165PubMed
45.
Zhang Y, Huypens P, Adamson AW, Chang JS, Henagan TM, Boudreau A, Lenard NR, Burk D, Klein J, Perwitz N, Shin J, Fasshauer M, Kralli A, Gettys TW (2009) Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha. J Biol Chem 284:32813–32826PubMed
46.
Yoshioka T, Inagaki K, Noguchi T, Sakai M, Ogawa W, Hosooka T, Iguchi H, Watanabe E, Matsuki Y, Hiramatsu R, Kasuga M (2009) Identification and characterization of an alternative promoter of the human PGC-1alpha gene. Biochem Biophys Res Commun 381:537–543PubMed
47.
Miura S, Kai Y, Kamei Y, Ezaki O (2008) Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology 149:4527–4533PubMed
48.
Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, Spiegelman BM (2012) A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151:1319–1331PubMedCentralPubMed
49.
Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, Spiegelman B, Montminy M (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179–183PubMed
50.
Handschin C, Rhee J, Lin J, Tarr PT, Spiegelman BM (2003) An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci U S A 100:7111–7116PubMedCentralPubMed
51.
Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG Jr, Xiong Y, Daniel KW, Floering L, Collins S (2005) p38 mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem 280:42731–42737PubMed
52.
Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, Williams RS, Yan Z (2005) Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem 280:19587–19593PubMed
53.
Jager S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 104:12017–12022PubMedCentralPubMed
54.
Hondares E, Mora O, Yubero P, de la Concepcion MR, Iglesias R, Giralt M, Villarroya F (2006) Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation. Endocrinology 147:2829–2838PubMed
55.
Hondares E, Rosell M, Diaz-Delfin J, Olmos Y, Monsalve M, Iglesias R, Villarroya F, Giralt M (2011) Peroxisome proliferator-activated receptor alpha (PPARalpha) induces PPARgamma coactivator 1alpha (PGC-1alpha) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16. J Biol Chem 286:43112–43122PubMed
56.
Daitoku H, Yamagata K, Matsuzaki H, Hatta M, Fukamizu A (2003) Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. Diabetes 52:642–649PubMed
57.
Czubryt MP, McAnally J, Fishman GI, Olson EN (2003) Regulation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha ) and mitochondrial function by MEF2 and HDAC5. Proc Natl Acad Sci U S A 100:1711–1716PubMedCentralPubMed
58.
Wang L, Liu J, Saha P, Huang J, Chan L, Spiegelman B, Moore DD (2005) The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes. Cell Metab 2:227–238PubMed
59.
Wu N, Yin L, Hanniman EA, Joshi S, Lazar MA (2009) Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha. Genes Dev 23:2201–2209PubMed
60.
Barres R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR (2009) Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab 10:189–198PubMed
61.
Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang C-Y, Krauss S, Mootha VK, Lowell BB, Spiegelman BM (2001) Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 8:971–982PubMed
62.
Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, Jaeger S, Erdjument-Bromage H, Tempst P, Spiegelman BM (2004) Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev 18:278–289PubMed
63.
Chang JS, Huypens P, Zhang Y, Black C, Kralli A, Gettys TW (2010) Regulation of NT-PGC-1alpha subcellular localization and function by protein kinase A-dependent modulation of nuclear export by CRM1. J Biol Chem 285:18039–18050PubMed
64.
Li X, Monks B, Ge Q, Birnbaum MJ (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447:1012–1016PubMed
65.
Anderson RM, Barger JL, Edwards MG, Braun KH, O'Connor CE, Prolla TA, Weindruch R (2008) Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response. Aging Cell 7:101–111PubMedCentralPubMed
66.
Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (2008) SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev 22:252–264PubMed
67.
Lerin C, Rodgers JT, Kalume DE, Kim SH, Pandey A, Puigserver P (2006) GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab 3:429–438PubMed
68.
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434:113–118PubMed
69.
Nemoto S, Fergusson MM, Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 280:16456–16460PubMed
70.
Canto C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20:98–105PubMedCentralPubMed
71.
Rytinki MM, Palvimo JJ (2009) SUMOylation attenuates the function of PGC-1alpha. J Biol Chem 284:26184–26193PubMed
72.
Hallberg M, Morganstein DL, Kiskinis E, Shah K, Kralli A, Dilworth SM, White R, Parker MG, Christian M (2008) A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. Mol Cell Biol 28:6785–6795PubMedCentralPubMed
73.
Housley MP, Udeshi ND, Rodgers JT, Shabanowitz J, Puigserver P, Hunt DF, Hart GW (2009) A PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose. J Biol Chem 284:5148–5157PubMed
74.
Teyssier C, Ma H, Emter R, Kralli A, Stallcup MR (2005) Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation. Genes Dev 19:1466–1473PubMed
75.
LeMoine CM, Lougheed SC, Moyes CD (2010) Modular evolution of PGC-1alpha in vertebrates. J Mol Evol 70:492–505PubMed
76.
Tiefenbock SK, Baltzer C, Egli NA, Frei C (2009) The Drosophila PGC-1 homologue Spargel coordinates mitochondrial activity to insulin signalling. Embo J 29:171-183
77.
Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A (2004) The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proc Natl Acad Sci U S A 101:6472–6477PubMedCentralPubMed
78.
Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (2003) The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem 278:9013–9018PubMed
79.
Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM (2004) Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A 101:6570–6575PubMedCentralPubMed
80.
Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119:121–135PubMed
81.
Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM, Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP (2005) PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3:e101PubMedCentralPubMed
82.
Sonoda J, Mehl IR, Chong LW, Nofsinger RR, Evans RM (2007) PGC-1beta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis. Proc Natl Acad Sci U S A 104:5223–5228PubMedCentralPubMed
83.
Lelliott CJ, Medina-Gomez G, Petrovic N, Kis A, Feldmann HM, Bjursell M, Parker N, Curtis K, Campbell M, Hu P, Zhang D, Litwin SE, Zaha VG, Fountain KT, Boudina S, Jimenez-Linan M, Blount M, Lopez M, Meirhaeghe A, Bohlooly YM, Storlien L, Stromstedt M, Snaith M, Oresic M, Abel ED, Cannon B, Vidal-Puig A (2006) Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance. PLoS Biol 4:e369PubMedCentralPubMed
84.
St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, Spiegelman BM (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278:26597–26603PubMed
85.
St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408PubMed
86.
Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, Spiegelman BM (2003) PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem 278:30843–30848PubMed
87.
Bagattin A, Hugendubler L, Mueller E (2010) Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis. Proc Natl Acad Sci U S A 107:20376–20381PubMedCentralPubMed
88.
Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801PubMed
89.
Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM (2007) The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 5:35–46PubMed
90.
Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, Tabata I (2002) Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem Biophys Res Commun 296:350–354PubMed
91.
Goto M, Terada S, Kato M, Katoh M, Yokozeki T, Tabata I, Shimokawa T (2000) cDNA cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats. Biochem Biophys Res Commun 274:350–354PubMed
92.
Pilegaard H, Saltin B, Neufer PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546:851–858PubMed
93.
Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO (2007) Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 282:194–199PubMed
94.
Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO, Kelly DP (2007) A role for the transcriptional coactivator PGC-1alpha in muscle refueling. J Biol Chem 282:36642–36651PubMed
95.
Wende AR, Huss JM, Schaeffer PJ, Giguere V, Kelly DP (2005) PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol 25:10684–10694PubMedCentralPubMed
96.
Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM (2008) Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake. J Appl Physiol 104:1304–1312PubMed
97.
Summermatter S, Baum O, Santos G, Hoppeler H, Handschin C (2010) Peroxisome proliferator-activated receptor gamma coactivator 1{alpha} (PGC-1{alpha}) promotes skeletal muscle lipid refueling in vivo by activating de novo lipogenesis and the pentose phosphate pathway. J Biol Chem 285:32793–32800PubMed
98.
Summermatter S, Troxler H, Santos G, Handschin C (2011) Coordinated balancing of muscle oxidative metabolism through PGC-1alpha increases metabolic flexibility and preserves insulin sensitivity. Biochem Biophys Res Commun 408:180–185PubMed
99.
Silveira LR, Pilegaard H, Kusuhara K, Curi R, Hellsten Y (2006) The contraction induced increase in gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species. Biochim Biophys Acta 1763:969–976PubMed
100.
Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT (2009) Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci U S A 106:20405–20410PubMedCentralPubMed
101.
Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, Spiegelman BM (2007) PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev 21:770–783PubMed
102.
Summermatter S, Thurnheer R, Santos G, Mosca B, Baum O, Treves S, Hoppeler H, Zorzato F, Handschin C (2012) Remodeling of calcium handling in skeletal muscle through PGC-1alpha: impact on force, fatigability, and fiber type. Am J Physiol Cell Physiol 302:C88–C99PubMed
103.
Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451:1008–1012PubMed
104.
Chinsomboon J, Ruas J, Gupta RK, Thom R, Shoag J, Rowe GC, Sawada N, Raghuram S, Arany Z (2009) The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle. Proc Natl Acad Sci U S A 106:21401–21406PubMedCentralPubMed
105.
Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM (2007) Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282:30014–30021PubMed
106.
Zechner C, Lai L, Zechner JF, Geng T, Yan Z, Rumsey JW, Collia D, Chen Z, Wozniak DF, Leone TC, Kelly DP (2011) Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity. Cell Metab 12:633–642
107.
Rowe GC, Jang C, Patten IS, Arany Z (2011) PGC-1beta regulates angiogenesis in skeletal muscle. Am J Physiol Endocrinol Metab 301:E155–E163PubMed
108.
Chang JH, Lin KH, Shih CH, Chang YJ, Chi HC, Chen SL (2006) Myogenic basic helix–loop–helix proteins regulate the expression of peroxisomal proliferator activated receptor-gamma coactivator-1alpha. Endocrinology 147:3093–3106PubMed
109.
Liu C, Li S, Liu T, Borjigin J, Lin JD (2007) Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 447:477–481PubMed
110.
Andrews JL, Zhang X, McCarthy JJ, McDearmon EL, Hornberger TA, Russell B, Campbell KS, Arbogast S, Reid MB, Walker JR, Hogenesch JB, Takahashi JS, Esser KA (2010) CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function. Proc Natl Acad Sci U S A 107:19090–19095PubMedCentralPubMed
111.
Speckmann B, Walter PL, Alili L, Reinehr R, Sies H, Klotz LO, Steinbrenner H (2008) Selenoprotein P expression is controlled through interaction of the coactivator PGC-1alpha with FoxO1a and hepatocyte nuclear factor 4alpha transcription factors. Hepatol 48:1998–2006
112.
Handschin C, Lin J, Rhee J, Peyer AK, Chin S, Wu PH, Meyer UA, Spiegelman BM (2005) Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell 122:505–515PubMed
113.
Shin DJ, Campos JA, Gil G, Osborne TF (2003) PGC-1alpha activates CYP7A1 and bile acid biosynthesis. J Biol Chem 278:50047–50052PubMed
114.
Li S, Arning E, Liu C, Vitvitsky V, Hernandez C, Banerjee R, Bottiglieri T, Lin JD (2009) Regulation of homocysteine homeostasis through the transcriptional coactivator PGC-1alpha. Am J Physiol Endocrinol Metab 296:E543–E548PubMed
115.
Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM (2005) Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 1:259–271PubMed
116.
Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM (2006) Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A 103:10086–10091PubMedCentralPubMed
117.
Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moreira AB, Doenst T, Medina-Gomez G, Litwin SE, Lelliott CJ, Vidal-Puig A, Abel ED (2011) PGC-1beta deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res 109:783–793PubMedCentralPubMed
118.
Lai L, Leone TC, Zechner C, Schaeffer PJ, Kelly SM, Flanagan DP, Medeiros DM, Kovacs A, Kelly DP (2008) Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev 22:1948–1961PubMed
119.
Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106:847–856PubMedCentralPubMed
120.
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM (2006) Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab 3:333–341PubMed
121.
Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, Chin S, Tempst P, Lazar MA, Spiegelman BM (2008) Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev 22:1397–1409PubMed
122.
Tadaishi M, Miura S, Kai Y, Kano Y, Oishi Y, Ezaki O (2011) Skeletal muscle-specific expression of PGC-1alpha-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake. PLoS One 6:e28290PubMedCentralPubMed
123.
Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E, Spiegelman BM (2012) FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26:271–281PubMed
124.
Scime A, Grenier G, Huh MS, Gillespie MA, Bevilacqua L, Harper ME, Rudnicki MA (2005) Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metab 2:283–295PubMed
125.
Pan D, Fujimoto M, Lopes A, Wang YX (2009) Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell 137:73–86PubMedCentralPubMed
126.
Kleiner S, Mepani RJ, Laznik D, Ye L, Jurczak MJ, Jornayvaz FR, Estall JL, Chatterjee Bhowmick D, Shulman GI, Spiegelman BM (2012) Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues. Proc Natl Acad Sci U S A 109:9635–9640PubMedCentralPubMed
127.
Yoon JC, Xu G, Deeney JT, Yang SN, Rhee J, Puigserver P, Levens AR, Yang R, Zhang CY, Lowell BB, Berggren PO, Newgard CB, Bonner-Weir S, Weir G, Spiegelman BM (2003) Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. Dev Cell 5:73–83PubMed
128.
Ling C, Del Guerra S, Lupi R, Ronn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S (2008) Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 51:615–622PubMedCentralPubMed
129.
Wareski P, Vaarmann A, Choubey V, Safiulina D, Liiv J, Kuum M, Kaasik A (2009) PGC-1{alpha} and PGC-1{beta} regulate mitochondrial density in neurons. J Biol Chem 284:21379–21385PubMed
130.
Liang H, Ward WF, Jang YC, Bhattacharya A, Bokov AF, Li Y, Jernigan A, Richardson A, Van Remmen H (2011) PGC-1alpha protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model. Muscle Nerve 44:947–956PubMed
131.
Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127:59–69PubMed
132.
Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 66:352–361PubMedCentralPubMed
133.
Ma D, Li S, Lucas EK, Cowell RM, Lin JD (2010) Neuronal inactivation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) protects mice from diet-induced obesity and leads to degenerative lesions. J Biol Chem 285:39087–39095PubMed
134.
Egger A, Samardzija M, Sothilingam V, Tanimoto N, Lange C, Salatino S, Fang L, Garcia-Garrido M, Beck S, Okoniewski MJ, Neutzner A, Seeliger MW, Grimm C, Handschin C (2012) PGC-1alpha determines light damage susceptibility of the murine retina. PLoS One 7:e31272PubMedCentralPubMed
135.
Kawakami Y, Tsuda M, Takahashi S, Taniguchi N, Esteban CR, Zemmyo M, Furumatsu T, Lotz M, Belmonte JC, Asahara H (2005) Transcriptional coactivator PGC-1alpha regulates chondrogenesis via association with Sox9. Proc Natl Acad Sci U S A 102:2414–2419PubMedCentralPubMed
136.
Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H, Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K (2009) Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med 15:259–266PubMed
137.
Vercauteren K, Pasko RA, Gleyzer N, Marino VM, Scarpulla RC (2006) PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth. Mol Cell Biol 26:7409–7419PubMedCentralPubMed
138.
Sacheck JM, Hyatt JP, Raffaello A, Jagoe RT, Roy RR, Edgerton VR, Lecker SH, Goldberg AL (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 21:140–155PubMed
139.
Adhihetty PJ, O'Leary MF, Chabi B, Wicks KL, Hood DA (2007) Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle. J Appl Physiol 102:1143–1151PubMed
140.
Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL, Spiegelman BM (2006) PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A 103:16260–16265PubMedCentralPubMed
141.
Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH (2007) The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest 117:3940–3951PubMedCentralPubMed
142.
Brault JJ, Jespersen JG, Goldberg AL (2010) Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy. J Biol Chem 285:19460–19471PubMed
143.
Wenz T, Diaz F, Spiegelman BM, Moraes CT (2008) Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 8:249–256PubMedCentralPubMed
144.
Wenz T, Diaz F, Hernandez D, Moraes CT (2009) Endurance exercise is protective for mice with mitochondrial myopathy. J Appl Physiol 106:1712–1719PubMed
145.
Chaturvedi RK, Adhihetty P, Shukla S, Hennessy T, Calingasan N, Yang L, Starkov A, Kiaei M, Cannella M, Sassone J, Ciammola A, Squitieri F, Beal MF (2009) Impaired PGC-1alpha function in muscle in Huntington's disease. Hum Mol Genet 18:3048–3065PubMed
146.
Crunkhorn S, Dearie F, Mantzoros C, Gami H, da Silva WS, Espinoza D, Faucette R, Barry K, Bianco AC, Patti ME (2007) Peroxisome proliferator activator receptor gamma coactivator-1 expression is reduced in obesity: potential pathogenic role of saturated fatty acids and p38 mitogen-activated protein kinase activation. J Biol Chem 282:15439–15450PubMed
147.
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman BM, Lander ES, Hirschhorn JN, Altshuler D, Groop LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273PubMed
148.
Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100:8466–8471PubMedCentralPubMed
149.
Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI (2005) Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115:3587–3593PubMedCentralPubMed
150.
Benton CR, Nickerson JG, Lally J, Han XX, Holloway GP, Glatz JF, Luiken JJ, Graham TE, Heikkila JJ, Bonen A (2008) Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. J Biol Chem 283:4228–4240PubMed
151.
Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM (2007) Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 117:3463–3474PubMedCentralPubMed
152.
Choi CS, Befroy DE, Codella R, Kim S, Reznick RM, Hwang YJ, Liu ZX, Lee HY, Distefano A, Samuel VT, Zhang D, Cline GW, Handschin C, Lin J, Petersen KF, Spiegelman BM, Shulman GI (2008) Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Natl Acad Sci U S A 105:19926–19931PubMedCentralPubMed
153.
Ling C, Poulsen P, Carlsson E, Ridderstrale M, Almgren P, Wojtaszewski J, Beck-Nielsen H, Groop L, Vaag A (2004) Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest 114:1518–1526PubMedCentralPubMed
154.
Ek J, Andersen G, Urhammer SA, Gaede PH, Drivsholm T, Borch-Johnsen K, Hansen T, Pedersen O (2001) Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus. Diabetologia 44:2220–2226PubMed
155.
Lacquemant C, Chikri M, Boutin P, Samson C, Froguel P (2002) No association between the G482S polymorphism of the proliferator-activated receptor- gamma coactivator-1 (PGC-1) gene and type II diabetes in French Caucasians. Diabetologia 45:602–603, discussion 4PubMed
156.
Nitz I, Ewert A, Klapper M, Doring F (2007) Analysis of PGC-1alpha variants Gly482Ser and Thr612Met concerning their PPARgamma2-coactivation function. Biochem Biophys Res Commun 353:481–486PubMed
157.
Kim JH, Shin HD, Park BL, Cho YM, Kim SY, Lee HK, Park KS (2005) Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population. Diabetologia 48:1323–1330PubMed
158.
Oberkofler H, Linnemayr V, Weitgasser R, Klein K, Xie M, Iglseder B, Krempler F, Paulweber B, Patsch W (2004) Complex haplotypes of the PGC-1alpha gene are associated with carbohydrate metabolism and type 2 diabetes. Diabetes 53:1385–1393PubMed
159.
Vianna CR, Huntgeburth M, Coppari R, Choi CS, Lin J, Krauss S, Barbatelli G, Tzameli I, Kim YB, Cinti S, Shulman GI, Spiegelman BM, Lowell BB (2006) Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance. Cell Metab 4:453–464PubMedCentralPubMed
160.
Andersen G, Wegner L, Yanagisawa K, Rose CS, Lin J, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Hansen T, Spiegelman BM, Pedersen O (2005) Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity. J Med Genet 42:402–407PubMed
161.
Ling C, Wegner L, Andersen G, Almgren P, Hansen T, Pedersen O, Groop L, Vaag A, Poulsen P (2007) Impact of the peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1beta expression and fibre type composition in human skeletal muscle. Diabetologia 50:1615–1620PubMed
162.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMed
163.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122PubMed
164.
Pagel-Langenickel I, Bao J, Joseph JJ, Schwartz DR, Mantell BS, Xu X, Raghavachari N, Sack MN (2008) PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle. J Biol Chem 283:22464–22472PubMed
165.
Handschin C (2009) The biology of PGC-1alpha and its therapeutic potential. Trends Pharmacol Sci 30:322–329PubMed
166.
Seruga B, Zhang H, Bernstein LJ, Tannock IF (2008) Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer 8:887–899PubMed
167.
Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384PubMed
168.
Hayden MS, Ghosh S (2012) NF-kappaB, the first quarter-century: remarkable progress and outstanding questions. Gene Dev 26:203–234PubMed
169.
Hoffmann A, Levchenko A, Scott ML, Baltimore D (2002) The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298:1241–1245PubMed
170.
Brown K, Park S, Kanno T, Franzoso G, Siebenlist U (1993) Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci U S A 90:2532–2536PubMedCentralPubMed
171.
Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A (1997) IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278:860–866PubMed
172.
Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293:1495–1499PubMed
173.
Xiao G, Harhaj EW, Sun SC (2001) NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell 7:401–409PubMed
174.
Coope HJ, Atkinson PG, Huhse B, Belich M, Janzen J, Holman MJ, Klaus GG, Johnston LH, Ley SC (2002) CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J 21:5375–5385PubMed
175.
Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR (2002) The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17:525–535PubMed
176.
Claudio E, Brown K, Park S, Wang H, Siebenlist U (2002) BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat Immunol 3:958–965PubMed
177.
Brenner DA, O'Hara M, Angel P, Chojkier M, Karin M (1989) Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature 337:661–663PubMed
178.
Wagner EF, Eferl R (2005) Fos/AP-1 proteins in bone and the immune system. Immunol Rev 208:126–140PubMed
179.
Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6:644–658PubMed
180.
Ryo A, Suizu F, Yoshida Y, Perrem K, Liou YC, Wulf G, Rottapel R, Yamaoka S, Lu KP (2003) Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell 12:1413–1426PubMed
181.
Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (2000) Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289:2350–2354PubMedCentralPubMed
182.
Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699PubMed
183.
Sizemore N, Lerner N, Dombrowski N, Sakurai H, Stark GR (2002) Distinct roles of the Ikappa B kinase alpha and beta subunits in liberating nuclear factor kappa B (NF-kappa B) from Ikappa B and in phosphorylating the p65 subunit of NF-kappa B. J Biol Chem 277:3863–3869PubMed
184.
Chew J, Biswas S, Shreeram S, Humaidi M, Wong ET, Dhillion MK, Teo H, Hazra A, Fang CC, Lopez-Collazo E, Bulavin DV, Tergaonkar V (2009) WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol 11:659–666PubMed
185.
Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, Delerive P, Fadel A, Chinetti G, Fruchart JC, Najib J, Maclouf J, Tedgui A (1998) Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393:790–793PubMed
186.
Marx N, Sukhova GK, Collins T, Libby P, Plutzky J (1999) PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99:3125–3131PubMed
187.
Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, Fruchart JC, Tedgui A, Haegeman G, Staels B (1999) Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274:32048–32054PubMed
188.
Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86PubMed
189.
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82PubMed
190.
Schule R, Rangarajan P, Kliewer S, Ransone LJ, Bolado J, Yang N, Verma IM, Evans RM (1990) Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62:1217–1226PubMed
191.
Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, Herrlich P (1990) Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62:1189–1204PubMed
192.
Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270:286–290PubMed
193.
Scheinman RI, Cogswell PC, Lofquist AK, Baldwin AS Jr (1995) Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 270:283–286PubMed
194.
Delerive P, De Bosscher K, Vanden Berghe W, Fruchart JC, Haegeman G, Staels B (2002) DNA binding-independent induction of IkappaBalpha gene transcription by PPARalpha. Mol Endocrinol 16:1029–1039PubMed
195.
Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG (1996) A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85:403–414PubMed
196.
Sheppard KA, Phelps KM, Williams AJ, Thanos D, Glass CK, Rosenfeld MG, Gerritsen ME, Collins T (1998) Nuclear integration of glucocorticoid receptor and nuclear factor-kappaB signaling by CREB-binding protein and steroid receptor coactivator-1. J Biol Chem 273:29291–29294PubMed
197.
Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, Hoffmann A, Subramaniam S, David M, Rosenfeld MG, Glass CK (2005) Molecular determinants of crosstalk between nuclear receptors and Toll-like receptors. Cell 122:707–721PubMedCentralPubMed
198.
Kassel O, Schneider S, Heilbock C, Litfin M, Gottlicher M, Herrlich P (2004) A nuclear isoform of the focal adhesion LIM-domain protein Trip6 integrates activating and repressing signals at AP-1- and NF-kappaB-regulated promoters. Genes Dev 18:2518–2528PubMed
199.
Rogatsky I, Luecke HF, Leitman DC, Yamamoto KR (2002) Alternate surfaces of transcriptional coregulator GRIP1 function in different glucocorticoid receptor activation and repression contexts. Proc Natl Acad Sci U S A 99:16701–16706PubMedCentralPubMed
200.
Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47–59PubMedCentralPubMed
201.
Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–763PubMedCentralPubMed
202.
Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME, Willson TM, Rosenfeld MG, Glass CK (2007) Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell 25:57–70PubMedCentralPubMed
203.
Lee JH, Park SM, Kim OS, Lee CS, Woo JH, Park SJ, Joe EH, Jou I (2009) Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-gamma-stimulated brain astrocytes. Mol Cell 35:806–817PubMed
204.
Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, Duriez P, Staels B (1999) Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 85:394–402PubMed
205.
Nissen RM, Yamamoto KR (2000) The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 14:2314–2329PubMed
206.
Luecke HF, Yamamoto KR (2005) The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression. Genes Dev 19:1116–1127PubMed
207.
Ito K, Barnes PJ, Adcock IM (2000) Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol 20:6891–6903PubMedCentralPubMed
208.
Ito K, Yamamura S, Essilfie-Quaye S, Cosio B, Ito M, Barnes PJ, Adcock IM (2006) Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J Exp Med 203:7–13PubMedCentralPubMed
209.
210.
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415PubMedCentralPubMed
211.
Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:665–668PubMed
212.
Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336PubMed
213.
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614PubMed
214.
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015–3025PubMedCentralPubMed
215.
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761PubMedCentralPubMed
216.
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461PubMed
217.
Rutkowski JM, Davis KE, Scherer PE (2009) Mechanisms of obesity and related pathologies: the macro- and microcirculation of adipose tissue. FEBS J 276:5738–5746PubMedCentralPubMed
218.
Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMed
219.
Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH (2008) Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7:485–495PubMedCentralPubMed
220.
Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, Pedersen AA, Kalthoff C, Tullin S, Sams A, Summer R, Walsh K (2010) Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem 285:6153–6160PubMed
221.
Kien CL (2009) Dietary interventions for metabolic syndrome: role of modifying dietary fats. Curr Diabet Rep 9:43–50
222.
Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447:1116–1120PubMedCentralPubMed
223.
Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A (2006) Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab 4:13–24PubMedCentralPubMed
224.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedCentralPubMed
225.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedCentralPubMed
226.
Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184PubMedCentralPubMed
227.
Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M, Yamauchi T, Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Nagai R, Kadowaki T (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281:26602–26614PubMed
228.
Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505PubMedCentralPubMed
229.
Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW Jr (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116:115–124PubMedCentralPubMed
230.
Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma IM, Olefsky JM (2009) Hematopoietic cell-specific deletion of Toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metab 10:419–429PubMedCentralPubMed
231.
Solinas G, Vilcu C, Neels JG, Bandyopadhyay GK, Luo JL, Naugler W, Grivennikov S, Wynshaw-Boris A, Scadeng M, Olefsky JM, Karin M (2007) JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 6:386–397PubMed
232.
Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198PubMed
233.
Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247PubMedCentralPubMed
234.
Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921–929PubMedCentralPubMed
235.
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939PubMedCentralPubMed
236.
Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P (2008) Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res 103:467–476PubMedCentralPubMed
237.
Elgazar-Carmon V, Rudich A, Hadad N, Levy R (2008) Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res 49:1894–1903PubMed
238.
Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920PubMed
239.
Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617PubMedCentralPubMed
240.
Ilan Y, Maron R, Tukpah AM, Maioli TU, Murugaiyan G, Yang K, Wu HY, Weiner HL (2010) Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci U S A 107:9765–9770PubMedCentralPubMed
241.
Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R (2012) Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab 15:518–533PubMed
242.
Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG (2008) Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 8:301–309PubMedCentralPubMed
243.
Hevener AL, Olefsky JM, Reichart D, Nguyen MT, Bandyopadyhay G, Leung HY, Watt MJ, Benner C, Febbraio MA, Nguyen AK, Folian B, Subramaniam S, Gonzalez FJ, Glass CK, Ricote M (2007) Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117:1658–1669PubMedCentralPubMed
244.
Baeza-Raja B, Munoz-Canoves P (2004) p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6. Mol Biol Cell 15:2013–2026PubMedCentralPubMed
245.
Canicio J, Ruiz-Lozano P, Carrasco M, Palacin M, Chien K, Zorzano A, Kaliman P (2001) Nuclear factor kappa B-inducing kinase and Ikappa B kinase-alpha signal skeletal muscle cell differentiation. J Biol Chem 276:20228–20233PubMed
246.
Conejo R, Valverde AM, Benito M, Lorenzo M (2001) Insulin produces myogenesis in C2C12 myoblasts by induction of NF-kappaB and downregulation of AP-1 activities. J Cell Physiol 186:82–94PubMed
247.
Lehtinen SK, Rahkila P, Helenius M, Korhonen P, Salminen A (1996) Down-regulation of transcription factors AP-1, Sp-1, and NF-kappa B precedes myocyte differentiation. Biochem Biophys Res Commun 229:36–43PubMed
248.
Dogra C, Changotra H, Mohan S, Kumar A (2006) Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-kappaB and degradation of MyoD protein. J Biol Chem 281:10327–10336PubMed
249.
Bakkar N, Wang J, Ladner KJ, Wang H, Dahlman JM, Carathers M, Acharyya S, Rudnicki MA, Hollenbach AD, Guttridge DC (2008) IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. J Cell Biol 180:787–802PubMed
250.
Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS Jr (1999) NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19:5785–5799PubMedCentralPubMed
251.
Dahlman JM, Wang J, Bakkar N, Guttridge DC (2009) The RelA/p65 subunit of NF-kappaB specifically regulates cyclin D1 protein stability: implications for cell cycle withdrawal and skeletal myogenesis. J Cell Biochem 106:42–51PubMed
252.
Wang H, Hertlein E, Bakkar N, Sun H, Acharyya S, Wang J, Carathers M, Davuluri R, Guttridge DC (2007) NF-kappaB regulation of YY1 inhibits skeletal myogenesis through transcriptional silencing of myofibrillar genes. Mol Cell Biol 27:4374–4387PubMedCentralPubMed
253.
Bakkar N, Ladner K, Canan BD, Liyanarachchi S, Bal NC, Pant M, Periasamy M, Li Q, Janssen PM, Guttridge DC (2012) IKKalpha and alternative NF-kappaB regulate PGC-1beta to promote oxidative muscle metabolism. J Cell Biol 196:497–511PubMed
254.
Ho RC, Hirshman MF, Li Y, Cai D, Farmer JR, Aschenbach WG, Witczak CA, Shoelson SE, Goodyear LJ (2005) Regulation of IkappaB kinase and NF-kappaB in contracting adult rat skeletal muscle. Am J Physiol Cell Physiol 289:C794–C801PubMed
255.
Ji LL, Gomez-Cabrera MC, Steinhafel N, Vina J (2004) Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat skeletal muscle. FASEB J 18:1499–1506PubMed
256.
Kramer HF, Goodyear LJ (2007) Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. J Appl Physiol 103:388–395PubMed
257.
Mourkioti F, Rosenthal N (2008) NF-kappaB signaling in skeletal muscle: prospects for intervention in muscle diseases. J Mol Med (Berl) 86:747–759
258.
Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298PubMed
259.
Mourkioti F, Kratsios P, Luedde T, Song YH, Delafontaine P, Adami R, Parente V, Bottinelli R, Pasparakis M, Rosenthal N (2006) Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J Clin Invest 116:2945–2954PubMedCentralPubMed
260.
Serrano AL, Baeza-Raja B, Perdiguero E, Jardi M, Munoz-Canoves P (2008) Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab 7:33–44PubMed
261.
Horsley V, Jansen KM, Mills ST, Pavlath GK (2003) IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell 113:483–494PubMed
262.
Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, Authier FJ, Dreyfus PA, Gherardi RK (2003) Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. J Cell Biol 163:1133–1143PubMed
263.
St Pierre BA, Tidball JG (1994) Macrophage activation and muscle remodeling at myotendinous junctions after modifications in muscle loading. Am J Pathol 145:1463–1471PubMed
264.
Tidball JG, Wehling-Henricks M (2007) Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol 578:327–336PubMed
265.
Villalta SA, Deng B, Rinaldi C, Wehling-Henricks M, Tidball JG (2011) IFN-gamma promotes muscle damage in the mdx mouse model of Duchenne muscular dystrophy by suppressing M2 macrophage activation and inhibiting muscle cell proliferation. J Immunol 187:5419–5428PubMedCentralPubMed
266.
Villalta SA, Rinaldi C, Deng B, Liu G, Fedor B, Tidball JG (2010) Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. Hum Mol Genet 20:790–805PubMed
267.
Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529(Pt 1):237–242PubMed
268.
Pedersen BK, Febbraio MA (2008) Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 88:1379–1406PubMed
269.
Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MA (2006) Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55:2688–2697PubMed
270.
Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79PubMed
271.
Keller P, Penkowa M, Keller C, Steensberg A, Fischer CP, Giralt M, Hidalgo J, Pedersen BK (2005) Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6. FASEB J 19:1181–1183PubMed
272.
Gleeson M (2007) Immune function in sport and exercise. J Appl Physiol 103:693–699PubMed
273.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403PubMed
274.
Fiatarone MA, O'Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330:1769–1775PubMed
275.
Tillerson JL, Caudle WM, Reveron ME, Miller GW (2003) Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson's disease. Neuroscience 119:899–911PubMed
276.
Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285:E433–E437PubMed
277.
Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 17:884–886PubMed
278.
Lancaster GI, Khan Q, Drysdale P, Wallace F, Jeukendrup AE, Drayson MT, Gleeson M (2005) The physiological regulation of toll-like receptor expression and function in humans. J Physiol 563:945–955PubMed
279.
Kim MS, Shigenaga JK, Moser AH, Feingold KR, Grunfeld C (2005) Suppression of estrogen-related receptor alpha and medium-chain acyl-coenzyme A dehydrogenase in the acute-phase response. J Lipid Res 46:2282–2288PubMed
280.
Feingold K, Kim MS, Shigenaga J, Moser A, Grunfeld C (2004) Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response. Am J Physiol Endocrinol Metab 286:E201–E207PubMed
281.
Planavila A, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M (2005) Atorvastatin prevents peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) downregulation in lipopolysaccharide-stimulated H9c2 cells. Biochim Biophys Acta 1736:120–127PubMed
282.
Palomer X, Alvarez-Guardia D, Rodriguez-Calvo R, Coll T, Laguna JC, Davidson MM, Chan TO, Feldman AM, Vazquez-Carrera M (2009) TNF-alpha reduces PGC-1alpha expression through NF-kappaB and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model. Cardiovasc Res 81:703–712PubMed
283.
Tran M, Tam D, Bardia A, Bhasin M, Rowe GC, Kher A, Zsengeller ZK, Akhavan-Sharif MR, Khankin EV, Saintgeniez M, David S, Burstein D, Karumanchi SA, Stillman IE, Arany Z, Parikh SM (2011) PGC-1alpha promotes recovery after acute kidney injury during systemic inflammation in mice. J Clin Invest 121:4003–4014PubMedCentralPubMed
284.
Sweeney TE, Suliman HB, Hollingsworth JW, Welty-Wolf KE, Piantadosi CA (2011) A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators in mice with staphylococcal aureus sepsis. PLoS One 6:e25249PubMedCentralPubMed
285.
Menconi MJ, Arany ZP, Alamdari N, Aversa Z, Gonnella P, O'Neal P, Smith IJ, Tizio S, Hasselgren PO (2010) Sepsis and glucocorticoids downregulate the expression of the nuclear cofactor PGC-1beta in skeletal muscle. Am J Physiol Endocrinol Metab 299:E533–E543PubMed
286.
Feingold KR, Moser A, Patzek SM, Shigenaga JK, Grunfeld C (2009) Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. J Lipid Res 50:2055–2063PubMed
287.
Yu XX, Barger JL, Boyer BB, Brand MD, Pan G, Adams SH (2000) Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics. Am J Physiol Endocrinol Metab 279:E433–E446PubMed
288.
Remels AH, Gosker HR, Bakker J, Guttridge DC, Schols AM, Langen RC (2013) Regulation of skeletal muscle oxidative phenotype by classical NF-kappaB signalling. Biochim Biophys Acta 1832:1313-1325
289.
Coll T, Jove M, Rodriguez-Calvo R, Eyre E, Palomer X, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M (2006) Palmitate-mediated downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha in skeletal muscle cells involves MEK1/2 and nuclear factor-kappaB activation. Diabetes 55:2779–2787PubMed
290.
Zhang Y, Liu C, Zhu L, Jiang X, Chen X, Qi X, Liang X, Jin S, Zhang P, Li Q, Wang D, Liu X, Zeng K, Zhang J, Xiang Y, Zhang CY (2007) PGC-1alpha inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells. PLoS One 2:e1137PubMedCentralPubMed
291.
Remels AH, Gosker HR, Schrauwen P, Hommelberg PP, Sliwinski P, Polkey M, Galdiz J, Wouters EF, Langen RC, Schols AM (2010) TNF-alpha impairs regulation of muscle oxidative phenotype: implications for cachexia? FASEB J : Off Publ Fed Am Soc Exp Biol 24:5052–5062
292.
Tang K, Wagner PD, Breen EC (2010) TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure. J Cell Physiol 222:320–327PubMed
293.
Remels AH, Schrauwen P, Broekhuizen R, Willems J, Kersten S, Gosker HR, Schols AM (2007) Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD. Eur Respir J : Off J Eur Soc Clin Respir Physiol 30:245–252
294.
Eisele PS, Salatino S, Sobek J, Hottiger MO, Handschin C (2013) The peroxisome proliferator-activated receptor gamma coactivator 1alpha/beta (PGC-1) coactivators repress the transcriptional activity of NF-kappaB in skeletal muscle cells. J Biol Chem 288:6589
295.
Kim HJ, Park KG, Yoo EK, Kim YH, Kim YN, Kim HS, Kim HT, Park JY, Lee KU, Jang WG, Kim JG, Kim BW, Lee IK (2007) Effects of PGC-1alpha on TNF-alpha-induced MCP-1 and VCAM-1 expression and NF-kappaB activation in human aortic smooth muscle and endothelial cells. Antioxid Redox Signal 9:301–307PubMed
296.
Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H (2012) Skeletal muscle PGC-1alpha is required for maintaining an acute LPS-induced TNFalpha response. PLoS One 7:e32222PubMedCentralPubMed
297.
Sonoda J, Laganiere J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, Lee CH, Giguere V, Evans RM (2007) Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev 21:1909–1920PubMed
298.
Shaul ME, Bennett G, Strissel KJ, Greenberg AS, Obin MS (2010) Dynamic, M2-like remodeling phenotypes of CD11c + adipose tissue macrophages during high-fat diet–induced obesity in mice. Diabetes 59:1171–1181PubMed
299.
Maitra U, Singh N, Gan L, Ringwood L, Li L (2009) IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species generation in macrophages by inducing NOX-1 transcription and Rac1 activation and suppressing the expression of antioxidative enzymes. J Biol Chem 284:35403–35411PubMed
300.
Ito S, Ansari P, Sakatsume M, Dickensheets H, Vazquez N, Donnelly RP, Larner AC, Finbloom DS (1999) Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 93:1456–1463PubMed
301.
Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D, Dieli F, Ghisletti S, Natoli G, De Baetselier P, Mantovani A, Sica A (2009) Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A 106:14978–14983PubMedCentralPubMed
302.
Liao X, Sharma N, Kapadia F, Zhou G, Lu Y, Hong H, Paruchuri K, Mahabeleshwar GH, Dalmas E, Venteclef N, Flask CA, Kim J, Doreian BW, Lu KQ, Kaestner KH, Hamik A, Clement K, Jain MK (2011) Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest 121:2736–2749PubMedCentralPubMed
303.
Mahabeleshwar GH, Kawanami D, Sharma N, Takami Y, Zhou G, Shi H, Nayak L, Jeyaraj D, Grealy R, White M, McManus R, Ryan T, Leahy P, Lin Z, Haldar SM, Atkins GB, Wong HR, Lingrel JB, Jain MK (2011) The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock. Immunity 34:715–728PubMedCentralPubMed
304.
Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 7:496–507PubMedCentralPubMed
305.
Suliman HB, Sweeney TE, Withers CM, Piantadosi CA (2010) Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis. J Cell Sci 123:2565–2575PubMed
306.
Mauro C, Leow SC, Anso E, Rocha S, Thotakura AK, Tornatore L, Moretti M, De Smaele E, Beg AA, Tergaonkar V, Chandel NS, Franzoso G (2011) NF-kappaB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. Nat Cell Biol 13:1272–1279PubMedCentralPubMed
307.
Piantadosi CA, Withers CM, Bartz RR, MacGarvey NC, Fu P, Sweeney TE, Welty-Wolf KE, Suliman HB (2011) Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. J Biol Chem 286:16374–16385PubMed
308.
Buler M, Aatsinki SM, Skoumal R, Komka Z, Toth M, Kerkela R, Georgiadi A, Kersten S, Hakkola J (2012) Energy-sensing factors coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and AMP-activated protein kinase control expression of inflammatory mediators in liver: induction of interleukin 1 receptor antagonist. J Biol Chem 287:1847–1860PubMed
309.
Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui Y, Hennighausen L, Gonzalez F, Rohrer J, Benninghoff AU, Hontecillas R (2004) Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterol 127:777–791
310.
Wang LH, Yang XY, Zhang X, Farrar WL (2007) Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPARgamma cross talk with NF-kappaB and C/EBP. Blood 110:4373–4384PubMed
311.
Morari J, Torsoni AS, Anhe GF, Roman EA, Cintra DE, Ward LS, Bordin S, Velloso LA (2010) The role of proliferator-activated receptor gamma coactivator-1alpha in the fatty-acid-dependent transcriptional control of interleukin-10 in hepatic cells of rodents. Metab: Clin Exp 59:215–223
312.
Alvarez-Guardia D, Palomer X, Coll T, Davidson MM, Chan TO, Feldman AM, Laguna JC, Vazquez-Carrera M (2010) The p65 subunit of NF-kappaB binds to PGC-1alpha, linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc Res 87:449–458PubMed
313.
Liang H, Balas B, Tantiwong P, Dube J, Goodpaster BH, O'Doherty RM, DeFronzo RA, Richardson A, Musi N, Ward WF (2009) Whole body overexpression of PGC-1alpha has opposite effects on hepatic and muscle insulin sensitivity. Am J Physiol Endocrinol Metab 296:E945–E954PubMed
314.
Yang J, Williams RS, Kelly DP (2009) Bcl3 interacts cooperatively with peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha to coactivate nuclear receptors estrogen-related receptor alpha and PPARalpha. Mol Cell Biol 29:4091–4102PubMedCentralPubMed
315.
Fink LN, Oberbach A, Costford SR, Chan KL, Sams A, Bluher M, Klip A (2013) Expression of anti-inflammatory macrophage genes within skeletal muscle correlates with insulin sensitivity in human obesity and type 2 diabetes. Diabetologia 56:1623–1628PubMed
316.
Fink LN, Costford SR, Lee YS, Jensen TE, Bilan PJ, Oberbach A, Bluher M, Olefsky JM, Sams A, Klip A (2013) Pro-inflammatory macrophages increase in skeletal muscle of high fat-Fed mice and correlate with metabolic risk markers in humans. Obesity doi:10.​1002/​oby.​20615
317.
Ikeda SI, Tamura Y, Kakehi S, Takeno K, Kawaguchi M, Watanabe T, Sato F, Ogihara T, Kanazawa A, Fujitani Y, Kawamori R, Watada H (2013) Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle. Biochem Biophys Res Commun doi:10.​1016/​j.​bbrc.​2013.​10.​005
318.
Sadana P, Park EA (2007) Characterization of the transactivation domain in the peroxisome-proliferator-activated receptor gamma co-activator (PGC-1). Biochem J 403:511–518PubMed
Metadaten
Titel
Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology
verfasst von
Petra S. Eisele
Christoph Handschin
Publikationsdatum
01.01.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 1/2014
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-013-0406-4

Weitere Artikel der Ausgabe 1/2014

Seminars in Immunopathology 1/2014 Zur Ausgabe

Review

Gut microbiome and metabolic diseases

Review

CEACAM1 loss links inflammation to insulin resistance in obesity and non-alcoholic steatohepatitis (NASH)

Review

Dendritic cells in atherosclerosis

Review

Microbiota and nonalcoholic steatohepatitis

Review

Immune cells and metabolic dysfunction

Introduction

Metabolic syndrome: variations on the theme of inflammation

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise