nach oben

Current Hypertension Reports

Erschienen in:

01.12.2015 | Hypertension and Metabolic Syndrome (J Sperati, Section Editor)

PPARγ Regulation in Hypertension and Metabolic Syndrome

verfasst von: Madeliene Stump, Masashi Mukohda, Chunyan Hu, Curt D. Sigmund

Erschienen in: Current Hypertension Reports | Ausgabe 12/2015

Einloggen, um Zugang zu erhalten

Abstract

Dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) activity leads to significant alterations in cardiovascular and metabolic regulation. This is most keenly observed by the metabolic syndrome-like phenotypes exhibited by patients carrying mutations in PPARγ. We will summarize recent findings regarding mechanisms of PPARγ regulation in the cardiovascular and nervous systems focusing largely on PPARγ in the smooth muscle, endothelium, and brain. Canonically, PPARγ exerts its effects by regulating the expression of target genes in these cells, and we will discuss mechanisms by which PPARγ targets in the vasculature regulate cardiovascular function. We will also discuss emerging evidence that PPARγ in the brain is a mediator of appetite and obesity. Finally, we will briefly review how novel PPARγ activators control posttranslational modifications of PPARγ and their prospects to offer new therapeutic options for treatment of metabolic diseases without the adverse side effects of thiazolidinediones which strongly activate transcriptional activity of PPARγ.

Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest. 2006;116(3):590–7.PubMedCentralCrossRefPubMed

Mansour M. The roles of peroxisome proliferator-activated receptors in the metabolic syndrome. Prog Mol Biol Transl Sci. 2014;121:217–66.CrossRefPubMed

Agostini M, Schoenmakers E, Mitchell C, Szatmari I, Savage D, Smith A, et al. Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance. Cell Metab. 2006;4(4):303–11.PubMedCentralCrossRefPubMed

Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402(6764):880–3.PubMed

Ludtke A, Buettner J, Wu W, Muchir A, Schroeter A, Zinn-Justin S, et al. Peroxisome proliferator-activated receptor-gamma C190S mutation causes partial lipodystrophy. J Clin Endocrinol Metabol. 2007;92(6):2248–55.CrossRef

Semple RK, Chatterjee VK, O’Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest. 2006;116(3):581–9.PubMedCentralCrossRefPubMed

Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M, et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes. 2003;52(4):910–7.CrossRefPubMed

Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med. 1998;339(14):953–9.CrossRefPubMed

Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004;53(8):2169–76.CrossRefPubMed

10.

Fonseca VA, Valiquett TR, Huang SM, Ghazzi MN, Whitcomb RW. Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled study. The Troglitazone Study Group. J Clin Endocrinol Metabol. 1998;83(9):3169–76.

11.

Ogihara T, Rakugi H, Ikegami H, Mikami H, Masuo K. Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. Am J Hypertens. 1995;8(3):316–20.CrossRefPubMed

12.

Charbonnel B, Dormandy J, Erdmann E, Massi-Benedetti M, Skene A, Group PRS. The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care. 2004;27(7):1647–53.CrossRefPubMed

13.

Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D’Agostino Sr RB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296(21):2572–81.CrossRefPubMed

14.

Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299(13):1561–73.CrossRefPubMed

15.

Chen Z, Ishibashi S, Perrey S, Osuga J, Gotoda T, Kitamine T, et al. Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL. Arterioscler Thromb Vasc Biol. 2001;21(3):372–7.CrossRefPubMed

16.

Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, Glass CK. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Investig. 2000;106(4):523–31.PubMedCentralCrossRefPubMed

17.

Bouhlel MA, Derudas B, Rigamonti E, Dievart R, Brozek J, Haulon S, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007;6(2):137–43.CrossRefPubMed

18.

Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007;447(7148):1116–20.PubMedCentralCrossRefPubMed

19.

Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature. 2005;437(7059):759–63.PubMedCentralCrossRefPubMed

20.

Wang P, Anderson PO, Chen S, Paulsson KM, Sjogren HO, Li S. Inhibition of the transcription factors AP-1 and NF-kappaB in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands. Int Immunopharmacol. 2001;1(4):803–12.CrossRefPubMed

21.

Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, et al. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Investig. 1996;97(7):1715–22.PubMedCentralCrossRefPubMed

22.

Rocha VZ, Libby P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol. 2009;6(6):399–409.CrossRefPubMed

23.

Qu A, Shah YM, Manna SK, Gonzalez FJ. Disruption of endothelial peroxisome proliferator-activated receptor gamma accelerates diet-induced atherogenesis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol. 2012;32(1):65–73.PubMedCentralCrossRefPubMed

24.

Hamblin M, Chang L, Zhang H, Yang K, Zhang J, Chen YE. Vascular smooth muscle cell peroxisome proliferator-activated receptor-gamma mediates pioglitazone-reduced vascular lesion formation. Arterioscler Thromb Vasc Biol. 2011;31(2):352–9.PubMedCentralCrossRefPubMed

25.

Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, et al. Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-gamma deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation. 2012;126(9):1067–78.PubMedCentralCrossRefPubMed

26.

Pelham CJ, Keen HL, Lentz SR, Sigmund CD. Dominant negative PPARgamma promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle. Am J Physiol Regul Integr Comp Physiol. 2013;304(9):R690–701.PubMedCentralCrossRefPubMed

27.

Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol. 2004;5(1):104–12.CrossRefPubMed

28.

Ryo A, Suizu F, Yoshida Y, Perrem K, Liou YC, Wulf G, et al. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell. 2003;12(6):1413–26.CrossRefPubMed

29.•

Hou Y, Moreau F, Chadee K. PPARgamma is an E3 ligase that induces the degradation of NFkappaB/p65. Nature Communications. 2012;3:1300. doi:10.1038/ncomms2270. New molecular evidence that PPARγ acts as an E3 ligase for NF-κB subunit, p65, resulting in inhibition of inflammation.

30.

Chetty VT, Sharma AM. Can PPARgamma agonists have a role in the management of obesity-related hypertension? Vasc Pharmacol. 2006;45(1):46–53.CrossRef

31.

Giles TD, Sander GE. Effects of thiazolidinediones on blood pressure. Curr Hypertens Rep. 2007;9(4):332–7.CrossRefPubMed

32.

Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.CrossRefPubMed

33.

Wilcox R, Bousser MG, Betteridge DJ, Schernthaner G, Pirags V, Kupfer S, et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04). Stroke. 2007;38(3):865–73.CrossRefPubMed

34.

Auclair M, Vigouroux C, Boccara F, Capel E, Vigeral C, Guerci B, et al. Peroxisome proliferator-activated receptor-gamma mutations responsible for lipodystrophy with severe hypertension activate the cellular renin-angiotensin system. Arterioscler Thromb Vasc Biol. 2013;33(4):829–38.CrossRefPubMed

35.

Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005;11(8):861–6.CrossRefPubMed

36.

Beyer AM, Baumbach GL, Halabi CM, Modrick ML, Lynch CM, Gerhold TD, et al. Interference with PPARgamma signaling causes cerebral vascular dysfunction, hypertrophy, and remodeling. Hypertension. 2008;51(4):867–71.PubMedCentralCrossRefPubMed

37.

Tsai YS, Kim HJ, Takahashi N, Kim HS, Hagaman JR, Kim JK, et al. Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPARgamma. J Clin Iinvestig. 2004;114(2):240–9.CrossRef

38.

Wang N, Yang G, Jia Z, Zhang H, Aoyagi T, Soodvilai S, et al. Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1. Cell Metab. 2008;8(6):482–91.CrossRefPubMed

39.

Chang L, Villacorta L, Zhang J, Garcia-Barrio MT, Yang K, Hamblin M, et al. Vascular smooth muscle cell-selective peroxisome proliferator-activated receptor-gamma deletion leads to hypotension. Circulation. 2009;119(16):2161–9.PubMedCentralCrossRefPubMed

40.

Marchesi C, Rehman A, Rautureau Y, Kasal DA, Briet M, Leibowitz A, et al. Protective role of vascular smooth muscle cell PPARgamma in angiotensin II-induced vascular disease. Cardiovasc Res. 2013;97(3):562–70.CrossRefPubMed

41.

Borges GR, Morgan DA, Ketsawatsomkron P, Mickle AD, Thompson AP, Cassell MD, et al. Interference with peroxisome proliferator-activated receptor-gamma in vascular smooth muscle causes baroreflex impairment and autonomic dysfunction. Hypertension. 2014;64(3):590–6.PubMedCentralCrossRefPubMed

42.

De Silva TM, Modrick ML, Ketsawatsomkron P, Lynch C, Chu Y, Pelham CJ, et al. Role of peroxisome proliferator-activated receptor-gamma in vascular muscle in the cerebral circulation. Hypertension. 2014;64(5):1088–93.PubMedCentralCrossRefPubMed

43.

Halabi CM, Beyer AM, de Lange WJ, Keen HL, Baumbach GL, Faraci FM, et al. Interference with PPAR gamma function in smooth muscle causes vascular dysfunction and hypertension. Cell Metab. 2008;7(3):215–26.PubMedCentralCrossRefPubMed

44.

Ketsawatsomkron P, Lorca RA, Keen HL, Weatherford ET, Liu X, Pelham CJ, et al. PPARgamma regulates resistance vessel tone through a mechanism involving RGS5-mediated control of protein kinase C and BKCa channel activity. Circ Res. 2012;111(11):1446–58.PubMedCentralCrossRefPubMed

45.

Pelham CJ, Ketsawatsomkron P, Groh S, Grobe JL, de Lange WJ, Ibeawuchi SR, et al. Cullin-3 regulates vascular smooth muscle function and arterial blood pressure via PPARgamma and RhoA/Rho-kinase. Cell Metab. 2012;16(4):462–72.PubMedCentralCrossRefPubMed

46.

Wakino S, Kintscher U, Liu Z, Kim S, Yin F, Ohba M, et al. Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in vascular smooth muscle cells. J Biol Chem. 2001;276(50):47650–7.CrossRefPubMed

47.

De Silva TM, Ketsawatsomkron P, Pelham C, Sigmund CD, Faraci FM. Genetic interference with peroxisome proliferator-activated receptor gamma in smooth muscle enhances myogenic tone in the cerebrovasculature via A Rho kinase-dependent mechanism. Hypertension. 2015;65(2):345–51.CrossRefPubMed

48.

Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482(7383):98–102.PubMedCentralCrossRefPubMed

49.•

McCormick JA, Yang CL, Zhang C, Davidge B, Blankenstein KI, Terker AS, et al. Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. J Clin Invest. 2014;124(11):4723–36. doi:10.1172/JCI76126. Loss of cullin-3 impairs WNK degradation and exerts renal toxic effects. PubMedCentralCrossRefPubMed

50.

Ibeawuchi SC, Agbor LN, Quelle FW, Sigmund CD. Hypertension causing mutations in cullin3 impair RhoA ubiquitination and augment association with substrate adaptors. J Biol Chem. 2015. doi:10.1074/jbc.M115.645358.PubMed

51.•

Schumacher FR, Siew K, Zhang J, Johnson C, Wood N, Cleary SE, et al. Characterisation of the cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia. EMBO Molecular Medicine. 2015;7:1285–306. A novel knockin mouse model expessing cullin-3 mutation recapitulates the phenotype of patients with PHAII. PubMedCentralCrossRefPubMed

52.

Ketsawatsomkron P, Sigmund CD. Molecular mechanisms regulating vascular tone by peroxisome proliferator activated receptor gamma. Curr Opin Nephrol Hypertens. 2015;24(2):123–30.CrossRefPubMed

53.

Nicol CJ, Adachi M, Akiyama TE, Gonzalez FJ. PPARgamma in endothelial cells influences high fat diet-induced hypertension. Am J Hypertens. 2005;18(4 Pt 1):549–56.CrossRefPubMed

54.

Kleinhenz JM, Kleinhenz DJ, You S, Ritzenthaler JD, Hansen JM, Archer DR, et al. Disruption of endothelial peroxisome proliferator-activated receptor-gamma reduces vascular nitric oxide production. Am J Physiol. 2009;297(5):H1647–54.

55.

Wan Y, Chong LW, Evans RM. PPAR-gamma regulates osteoclastogenesis in mice. Nat Med. 2007;13(12):1496–503.CrossRefPubMed

56.

Yin KJ, Fan Y, Hamblin M, Zhang J, Zhu T, Li S, et al. KLF11 mediates PPARgamma cerebrovascular protection in ischaemic stroke. Brain. 2013;136(Pt 4):1274–87.PubMedCentralCrossRefPubMed

57.

Beyer AM, de Lange WJ, Halabi CM, Modrick ML, Keen HL, Faraci FM, et al. Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet. Circ Res. 2008;103(6):654–61.PubMedCentralCrossRefPubMed

58.

Kanda T, Brown JD, Orasanu G, Vogel S, Gonzalez FJ, Sartoretto J, et al. PPARgamma in the endothelium regulates metabolic responses to high-fat diet in mice. J Clin Invest. 2009;119(1):110–24.PubMedCentralPubMed

59.•

Wong WT, Tian XY, Xu A, Yu J, Lau CW, Hoo RL, et al. Adiponectin is required for PPARgamma-mediated improvement of endothelial function in diabetic mice. Cell Metab. 2011;14(1):104–15. The first evidence to show the importance of adiponectin in PPARγ-mediated protective effects in the endothelium of both diabetic and obesity models. CrossRefPubMed

60.•

Komura N, Maeda N, Mori T, Kihara S, Nakatsuji H, Hirata A, et al. Adiponectin protein exists in aortic endothelial cells. PLoS ONE. 2013;8(8):e71271. The first evidence to show that adiponectin is expressed in aortic endothelial cells. PubMedCentralCrossRefPubMed

61.

Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation. 2013;127(22):2209–21.CrossRefPubMed

62.

Larsen PJ, Jensen PB, Sorensen RV, Larsen LK, Vrang N, Wulff EM, et al. Differential influences of peroxisome proliferator-activated receptors gamma and -alpha on food intake and energy homeostasis. Diabetes. 2003;52(9):2249–59.CrossRefPubMed

63.

Shimizu H, Tsuchiya T, Sato N, Shimomura Y, Kobayashi I, Mori M. Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients. Diabetes Care. 1998;21(9):1470–4.CrossRefPubMed

64.

Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79(7):1147–56.CrossRefPubMed

65.

Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4(4):611–7.CrossRefPubMed

66.

Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994;135(2):798–800.PubMed

67.

Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care. 1999;22(2):288–93.CrossRefPubMed

68.

Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, et al. PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization. Proc Natl Acad Sci. 2009;106(52):22504–9.PubMedCentralCrossRefPubMed

69.

Burant CF, Sreenan S, Hirano K, Tai TA, Lohmiller J, Lukens J, et al. Troglitazone action is independent of adipose tissue. J Clin Invest. 1997;100(11):2900–8.PubMedCentralCrossRefPubMed

70.

He W, Barak Y, Hevener A, Olson P, Liao D, Le J, et al. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci. 2003;100(26):15712–7.PubMedCentralCrossRefPubMed

71.

Festuccia WT, Oztezcan S, Laplante M, Berthiaume M, Michel C, Dohgu S, et al. Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology. 2008;149(5):2121–30.CrossRefPubMed

72.

Sarruf DA, Yu F, Nguyen HT, Williams DL, Printz RL, Niswender KD, et al. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis. Endocrinology. 2009;150(2):707–12.PubMedCentralCrossRefPubMed

73.

Ryan KK, Li B, Grayson BE, Matter EK, Woods SC, Seeley RJ. A role for central nervous system PPAR-gamma in the regulation of energy balance. Nat Med. 2011;17(5):623–6.PubMedCentralCrossRefPubMed

74.

Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G, et al. Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nat Med. 2011;17(5):618–22.PubMedCentralCrossRefPubMed

75.

Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70.CrossRefPubMed

76.

Myers Jr MG, Burant CF. PPAR-gamma action: it’s all in your head. Nat Med. 2011;17(5):544–5.CrossRefPubMed

77.

Woods SC, Seeley RJ, Porte Jr D, Schwartz MW. Signals that regulate food intake and energy homeostasis. Science. 1998;280(5368):1378–83.CrossRefPubMed

78.

Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736–49.CrossRefPubMed

79.

Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, et al. Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med. 2011;17(9):1121–7.PubMedCentralCrossRefPubMed

80.•

Long L, Toda C, Jeong JK, Horvath TL, Diano S. PPARgamma ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. The Journal of Clinical Investigation. 2014;124:4017–27. Deletion of PPARγ in POMC neurons leads to DIO resistance and improved insulin sensitivity. PubMedCentralCrossRefPubMed

81.•

Garretson JT, Teubner BJ, Grove KL, Vazdarjanova A, Ryu V, Bartness TJ. Peroxisome proliferator-activated receptor gamma controls ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus. J Neurosci. 2015;35(11):4571–81. The first evidence that starvation leads to upregulation of AgRP/NPY expression through PPARγ. PubMedCentralCrossRefPubMed

82.

Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2004;27(1):256–63.CrossRefPubMed

83.

Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302(14):1573–9.PubMedCentralCrossRefPubMed

84.

Faillie JL, Petit P, Montastruc JL, Hillaire-Buys D. Scientific evidence and controversies about pioglitazone and bladder cancer: which lessons can be drawn? Drug Saf. 2013.

85.

Rangwala SM, Lazar MA. The dawn of the SPPARMs? Sci: Signal Transduct Knowl Environ. 2002;2002(121):e9.

86.

Choi JH, Banks AS, Estall JL, Kajimura S, Bostrom P, Laznik D, et al. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature. 2010;466(7305):451–6.PubMedCentralCrossRefPubMed

87.

Choi JH, Banks AS, Kamenecka TM, Busby SA, Chalmers MJ, Kumar N, et al. Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated phosphorylation. Nature. 2011;477(7365):477–81.PubMedCentralCrossRefPubMed

88.

Amato AA, Rajagopalan S, Lin JZ, Carvalho BM, Figueira AC, Lu J, et al. GQ-16, a novel peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, promotes insulin sensitization without weight gain. J Biol Chem. 2012;287(33):28169–79.PubMedCentralCrossRefPubMed

89.

Liu C, Feng T, Zhu N, Liu P, Han X, Chen M, et al. Identification of a novel selective agonist of PPARgamma with no promotion of adipogenesis and less inhibition of osteoblastogenesis. Sci Rep. 2015;5:9530.PubMedCentralCrossRefPubMed

90.

Nedergaard J, Petrovic N, Lindgren EM, Jacobsson A, Cannon B. PPARgamma in the control of brown adipocyte differentiation. Biochimica. 2005;1740(2):293–304.

91.

Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of PPARgamma. Cell. 2012;150(3):620–32.PubMedCentralCrossRefPubMed

92.

Quelle FW, Sigmund CD. PPARgamma: no SirT, no service. Circ Res. 2013;112(3):411–4.PubMedCentralCrossRefPubMed

93.

Shimizu M, Yamashita D, Yamaguchi T, Hirose F, Osumi T. Aspects of the regulatory mechanisms of PPAR functions: analysis of a bidirectional response element and regulation by sumoylation. Mol Cell Biochem. 2006;286(1-2):33–42.CrossRefPubMed

Titel: PPARγ Regulation in Hypertension and Metabolic Syndrome
verfasst von: Madeliene Stump
Masashi Mukohda
Chunyan Hu
Curt D. Sigmund
Publikationsdatum: 01.12.2015
Verlag: Springer US
Erschienen in: Current Hypertension Reports / Ausgabe 12/2015
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI: https://doi.org/10.1007/s11906-015-0601-x

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

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2015

Predictors of Renal Denervation Efficacy in the Treatment of Resistant Hypertension

Neurohumoral Integration of Cardiovascular Function by the Lamina Terminalis

Dysregulated Blood Pressure: Can Regulating Emotions Help?

Interventions to Improve Medication Adherence in Hypertensive Patients: Systematic Review and Meta-analysis