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Current Obesity Reports
Erschienen in: Current Obesity Reports 3/2019

27.03.2019 | Obesity Treatment (CM Apovian, Section Editor)

Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity

verfasst von: Heather L. Caslin, Alyssa H. Hasty

Erschienen in: Current Obesity Reports | Ausgabe 3/2019

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Abstract

Purpose of Review

Research over the past decade has shown that immunologic and metabolic pathways are intricately linked. This burgeoning field of immunometabolism includes intrinsic and extrinsic pathways and is known to be associated with obesity-accelerated metabolic disease. Intrinsic immunometabolism includes the study of fuel utilization and bioenergetic pathways that influence immune cell function. Extrinsic immunometabolism includes the study of immune cells and products that influence systemic metabolism.

Recent Findings

Th2 immunity, macrophage iron handling, adaptive immune memory, and epigenetic regulation of immunity, which all require intrinsic metabolic changes, play a role in systemic metabolism and metabolic function, linking the two arms of immunometabolism. Together, this suggests that targeting intrinsic immunometabolism can directly affect immune function and ultimately systemic metabolism.

Summary

We highlight important questions for future basic research that will help improve translational research and provide therapeutic targets to help establish new treatments for obesity and associated metabolic disorders.
Literatur
1.
Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA. 2016;315:2284–91.CrossRefPubMed
2.
3.
4.
Courcoulas AP, Yanovski SZ, Bonds D, Eggerman TL, Horlick M, Staten MA, et al. Long-term outcomes of bariatric surgery: a National Institutes of Health Symposium. JAMA Surg. 2014;149:1323–9.CrossRefPubMedPubMedCentral
5.
Trandafir LM, Temneanu OR. Pre and post-natal risk and determination of factors for child obesity. J Med Life. 2016;9:386–91.PubMedPubMedCentral
6.
Kim GW, Lin JE, Blomain ES, Waldman SA. Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther. 2013;95:53–66.CrossRefPubMed
7.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.CrossRefPubMedPubMedCentral
8.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.CrossRefPubMedPubMedCentral
9.
10.
11.
•• Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG, Stienstra R. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia. 2018;61:942–53 This is the first study to metabolically phenotype ATM. ATM from HFD-fed mice had enhanced glycolytic metabolism and OX PHOS supporting the research which shows that they are different from M1 (glycolytic) or M2 (oxidative) cells. It is interesting that both metabolic pathways are enhanced in one cell type. The authors showed that cytokine production was directly tied to elevated glycolytic metabolism (and not dependent on HIF-1), and hypothesize that OX PHOS contributes to lysosomal biogenesis or phagocytosis. CrossRefPubMedPubMedCentral
12.
13.
14.
Bolus WR, Hasty AH. Contributions of innate type 2 inflammation to adipose function. J Lipid Res. 2018:jlr.R085993.
15.
Xia S, Sha H, Yang L, Ji Y, Ostrand-Rosenberg S, Qi L. Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem. 2011;286:23591–9.CrossRefPubMedPubMedCentral
16.
17.
Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, et al. Metabolic dysfunction drives a mechanistically distinct pro-inflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014;20:614–25.CrossRefPubMedPubMedCentral
18.
Cho KW, Zamarron BF, Muir LA, Singer K, Porsche CE, DelProposto JB, et al. Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance. J Immunol. 2016;197:3650–61.CrossRefPubMed
19.
Gutierrez DA, Kennedy A, Orr JS, Anderson EK, Webb CD, Gerrald WK, et al. Aberrant accumulation of undifferentiated myeloid cells in the adipose tissue of CCR2-deficient mice delays improvements in insulin sensitivity. Diabetes. 2011;60:2820–9.CrossRefPubMedPubMedCentral
20.
Bolus WR, Gutierrez DA, Kennedy AJ, Anderson-Baucum EK, Hasty AH. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue. J Leukoc Biol. 2015;98:467–77.CrossRefPubMedPubMedCentral
21.
Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116:115–24.CrossRefPubMed
22.
Kim J, Chung K, Choi C, Beloor J, Ullah I, Kim N, et al. Silencing CCR2 in macrophages alleviates adipose tissue inflammation and the associated metabolic syndrome in dietary obese mice. Mol Ther Nucleic Acids. 2016;5:e280.CrossRefPubMedPubMedCentral
23.
Orr JS, Kennedy AJ, Hill AA, Anderson-Baucum EK, Hubler MJ, Hasty AH. CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice. Physiol Rep. 2016;4:e12971.CrossRefPubMedPubMedCentral
24.
Kennedy A, Webb CD, Hill AA, Gruen ML, Jackson LG, Hasty AH. Loss of CCR5 results in glucose intolerance in diet-induced obese mice. Am J Physiol Endocrinol Metab. 2013;305:E897–906.CrossRefPubMedPubMedCentral
25.
Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, et al. IL-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res. 2010;107:650–8.CrossRefPubMedPubMedCentral
26.
Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Morimoto M, Hayashi N, et al. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol. 2008;20:791–800.CrossRefPubMed
27.
Harmon DB, Srikakulapu P, Kaplan JL, Oldham SN, McSkimming C, Garmey JC, et al. Protective role for B-1b B cells and IgM in obesity-associated inflammation, glucose intolerance, and insulin resistance significance. Arterioscler Thromb Vasc Biol. 2016;36:682–91.CrossRefPubMedPubMedCentral
28.
Ilan Y, Maron R, Tukpah A-M, Maioli TU, Murugaiyan G, Yang K, et al. Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. PNAS. 2010;107:9765–70.CrossRefPubMedPubMedCentral
29.
Kosteli A, Sugaru E, Haemmerle G, Martin JF, Lei J, Zechner R, et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest. 2010;120:3466–79.CrossRefPubMedPubMedCentral
30.
Anderson EK, Gutierrez DA, Kennedy A, Hasty AH. Weight cycling increases T-cell accumulation in adipose tissue and impairs systemic glucose tolerance. Diabetes. 2013;62:3180–8.CrossRefPubMedPubMedCentral
31.
Zamarron BF, Mergian TA, Cho KW, Martinez-Santibanez G, Luan D, Singer K, et al. Macrophage proliferation sustains adipose tissue inflammation in formerly obese mice. Diabetes. 2017;66:392–406.
32.
33.
Loftus RM, Finlay DK. Immunometabolism: cellular metabolism turns immune regulator. J Biol Chem. 2016;291:1–10.CrossRefPubMed
34.
Norata GD, Caligiuri G, Chavakis T, Matarese G, Netea MG, Nicoletti A, et al. The cellular and molecular basis of translational immunometabolism. Immunity. 2015;43:421–34.CrossRefPubMed
35.
36.
37.
Bantug GR, Galluzzi L, Kroemer G, Hess C. The spectrum of T cell metabolism in health and disease. Nat Rev Immunol. 2017;18:19–34.CrossRefPubMed
38.
Wahl DR, Byersdorfer CA, Ferrara JLM, Opipari AW, Glick GD. Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol Rev. 2012;249:104–15.CrossRefPubMedPubMedCentral
39.
• Porter L, Toepfner N, Bashant KR, Guck J, Ashcroft M, Farahi N, et al. Metabolic profiling of human eosinophils. Front Immunol. 2018;9:1404. This study shows that human eosinophils have high glycolytic metabolism similar to neutrophils, however eosinophils also have elevated OX PHOS. Like the study by Boutens, et al above, it is interesting that eosinophils use both energy generating pathways at a substantial rate.
40.
Yang J-Q, Kalim KW, Li Y, Zhang S, Hinge A, Filippi M-D, et al. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. 2016;137:231–245.e4.CrossRefPubMed
41.
Pelgrom LR, Everts B. Metabolic control of type 2 immunity. Eur J Immunol. 2017;47:1266–75.CrossRefPubMed
42.
Wang T, Liu H, Lian G, Zhang S-Y, Wang X, Jiang C. HIF1α-induced glycolysis metabolism is essential to the activation of inflammatory macrophages. Mediat Inflamm. 2017;2017:1–10.
43.
Peng M, Yin N, Chhangawala S, Xu K, Leslie CS, Li MO. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016;354:481–4.CrossRefPubMedPubMedCentral
44.
Phan AT, Doedens AL, Palazon A, Tyrakis PA, Cheung KP, Johnson RS, et al. Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection. Immunity. 2016;45:1024–37.CrossRefPubMedPubMedCentral
45.
Wu M, Ye W, Zheng Y, Zhang S. Oxamate enhances the anti-inflammatory and insulin-sensitizing effects of metformin in diabetic mice. Pharmacology. 2017;100:218–28.CrossRefPubMed
46.
Ye W, Zheng Y, Zhang S, Yan L, Cheng H, Wu M. Oxamate improves glycemic control and insulin sensitivity via inhibition of tissue lactate production in db/db mice. PLoS One. 2016;11:e0150303.
47.
Woo S-L, Xu H, Li H, Zhao Y, Hu X, Zhao J, et al. Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. PLoS One. 2014;9:e91111.CrossRefPubMedPubMedCentral
48.
Caslin HL, Taruselli MT, Haque T, Pondicherry N, Baldwin EA, Barnstein BO, et al. Inhibiting glycolysis and ATP production attenuates IL-33-mediated mast cell function and peritonitis. Front Immunol. 2018;9:3026. eCollection 2018.
49.
Go Y, Jeong JY, Jeoung NH, Jeon J-H, Park B-Y, Kang H-J, et al. Inhibition of pyruvate dehydrogenase kinase 2 protects against hepatic steatosis through modulation of tricarboxylic acid cycle anaplerosis and ketogenesis. Diabetes. 2016;65:2876–87.CrossRefPubMed
50.
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;447:1116–20.CrossRefPubMedPubMedCentral
51.
Kawano Y, Nakae J, Watanabe N, Fujisaka S, Iskandar K, Sekioka R, et al. Loss of Pdk1-Foxo1 signaling in myeloid cells predisposes to adipose tissue inflammation and insulin resistance. Diabetes. 2012;61:1935–48.CrossRefPubMedPubMedCentral
52.
Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, et al. Adipocyte-derived Th2 cytokines and myeloid PPAR delta regulate macrophage polarization and insulin sensitivity. Cell Metab. 2008;7:485–95.CrossRefPubMedPubMedCentral
53.
Johnson AR, Qin Y, Cozzo AJ, Freemerman AJ, Huang MJ, Zhao L, et al. Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Mol Metab. 2016;5:506–26.CrossRefPubMedPubMedCentral
54.
Dayton TL, Gocheva V, Miller KM, Israelsen WJ, Bhutkar A, Clish CB, et al. Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma. Genes Dev. 2016;30:1020–33.CrossRefPubMedPubMedCentral
55.
Kong Q, Li N, Cheng H, Zhang X, Cao X, Qi T, et al. HSPA12A is a novel player in nonalcoholic steatohepatitis via promoting nuclear PKM2-mediated M1 macrophage polarization. Diabetes. 2019;68:361–76.CrossRefPubMed
56.
Sheng W-Y, Wang T-CV. Proteomic analysis of the differential protein expression reveals nuclear GAPDH in activated T lymphocytes. PLoS One. 2009;4:e6322.CrossRefPubMedPubMedCentral
57.
• Freemerman AJ, Zhao L, Pingili AK, Teng B, Cozzo AJ, Fuller AM, et al. Myeloid Slc2a1 -deficient murine model revealed macrophage activation and metabolic phenotype are fueled by GLUT1. J Immunol. 2019:202:1265–-1286:ji1800002.This study shows that BMDM from myeloid-specific glucose transporter GLUT1 (Slc2a1) deficient mice had reduced glycolysis (as expected), and reduced maximal respiratory capacity, despite compensatory oleate and glutamine metabolism. Myeloid Slc2a1M deficiency was not protective for obesity-induced metabolic dysregulation and induced unstable atheroma formation in an Ldlr-/- atherosclerosis model, which suggests that this deficiency affects phagocytic capacity more than cytokine production. This was the first study to show that blunting glycolysis in macrophages does not affect systemic metabolism and reiterates the importance of examining many functional parameters when modulating metabolism.
58.
Kim T, Moore JF, Sharer JD, Yang K, Wood PA, Yang Q. Carnitine palmitoyltransferase 1b deficient mice develop severe insulin resistance after prolonged high fat diet feeding. J Diabetes Metab. 2014;5:1000401.
59.
Kim T, He L, Johnson M, Li Y, Zeng L, Ding Y, et al. Carnitine palmitoyltransferase 1b deficiency protects mice from diet-induced insulin resistance. J Diab Metab. 2014;05:361.
60.
• Divakaruni AS, Hsieh WY, Minarrieta L, Duong TN, Kim KKO, Desousa BR, et al. Etomoxir inhibits macrophage polarization by disrupting CoA homeostasis. Cell Metab. 2018;28:490–503.e7 Etomoxir has long been used to inhibit carnitine palmitoyltransferase-1 and make inferences about FAO. However, many studies have used concentrations of etomoxir that far exceed what is required to inhibit enzyme activity (EC90 < 3 μM), and many published results are therefore due to off target effects. This study showed that etomoxir blocks M2 polarization even in the absence of Cpt1a and Cpt2 expression, and that OX PHOS is dispensable for M(IL-4). Interestingly, the reduced polarization was traced to depletion of intracellular free coenzyme A (CoA). This study is the first to reveal the off target effects of etomoxir and dispute prior studies which link M2 polarization to FAO. CrossRefPubMedPubMedCentral
61.
Molofsky AB, Nussbaum JC, Liang H-E, Van Dyken SJ, Cheng LE, Mohapatra A, et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210:535–49.CrossRefPubMedPubMedCentral
62.
Wu D, Molofsky AB, Liang H-E, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332:243–7.CrossRefPubMedPubMedCentral
63.
Bolus WR, Peterson KR, Hubler MJ, Kennedy AJ, Gruen ML, Hasty AH. Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments. Mol Metab. 2018;8:86–95.CrossRefPubMed
64.
Bolus WR. Diversity of adipose tissue immune cells: are all eosinophils created equal? BioEssays. 2018;40:1800150.CrossRef
65.
Lee C-F, Lo Y-C, Cheng C-H, Furtmüller GJ, Oh B, Andrade-Oliveira V, et al. Preventing allograft rejection by targeting immune metabolism. Cell Rep. 2015;13:760–70.CrossRefPubMedPubMedCentral
66.
Calvaresi EC, Granchi C, Tuccinardi T, Di Bussolo V, Huigens RW, Lee HY, et al. Dual targeting of the Warburg effect with glucose-conjugated lactate dehydrogenase inhibitor. Chembiochem. 2013;14:2263–7.CrossRefPubMedPubMedCentral
67.
68.
Aouadi M, Tencerova M, Vangala P, Yawe JC, Nicoloro SM, Amano SU, et al. Gene silencing in adipose tissue macrophages regulates whole-body metabolism in obese mice. PNAS. 2013;110:8278–83.CrossRefPubMedPubMedCentral
69.
70.
Orr JS, Kennedy A, Anderson-Baucum EK, Webb CD, Fordahl SC, Erikson KM, et al. Obesity alters adipose tissue macrophage iron content and tissue iron distribution. Diabetes. 2014;63:421–32.CrossRefPubMedPubMedCentral
71.
Clementi AH, Gaudy AM, van Rooijen N, Pierce RH, Mooney RA. Loss of Kupffer cells in diet-induced obesity is associated with increased hepatic steatosis, STAT3 signaling, and further decreases in insulin signaling. Biochim Biophys Acta. 2009;1792:1062–72.CrossRefPubMedPubMedCentral
72.
Mayoral Monibas R, Johnson AMF, Osborn O, Traves PG, Mahata SK. Distinct hepatic macrophage populations in lean and obese mice. Front Endocrinol. 2016;7:152.
73.
Kaempfer T, Duerst E, Gehrig P, Roschitzki B, Rutishauser D, Grossmann J, et al. Extracellular hemoglobin polarizes the macrophage proteome toward Hb-clearance, enhanced antioxidant capacity and suppressed HLA class 2 expression. J Proteome Res. 2011;10:2397–408.CrossRefPubMed
74.
Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and iron: current questions. Expert Rev Hematol. 2017;10:65–79.CrossRefPubMed
75.
Hubler MJ, Erikson KM, Kennedy AJ, Hasty AH. MFe hi adipose tissue macrophages compensate for tissue iron perturbations in mice. Am J Physiol Cell Physiol. 2018;315:C319–29.CrossRefPubMedPubMedCentral
76.
Dong H, Bullock TNJ. Metabolic influences that regulate dendritic cell function in tumors. Front Immunol. 2014;5:24.
77.
•• Zou J, Lai B, Zheng M, Chen Q, Jiang S, Song A, et al. CD4+ T cells memorize obesity and promote weight regain. Cell Mol Immunol. 2018;15:630–9 This study showed that previously obese mice regain weight much faster than mice that have never been obese, a phenotype that lasts at least 2 months. This memory was attenuated by dexamethasone treatment and in immunodeficient Rag1-/- and H2A-/- mice. Memory was restored after introducing CD4+ T cells from previously obese mice in the Rag1-/-, and depletion of CD4+ T cells led to obesity memory ablation. This is the first study to show that CD4+ T cells modulate weight cycling- associated metabolic parameters. CrossRefPubMed
78.
•• McDonnell WJ, Koethe JR, Mallal SA, Pilkinton MA, Kirabo A, Ameka MK, et al. High CD8 T-cell receptor clonality and altered CDR3 properties are associated with elevated isolevuglandins in adipose tissue during diet-induced obesity. Diabetes. 2018;67:2361–76 This study showed that HFD feeding reduced TCR diversity and increased TCR CDR3 regions with positively-charged and less polar amino acids in AT CD8 + T cells. Moreover, negatively-charged and nonpolar isolevuglandin-adducted protein species were higher in AT macrophages of HFD-fed mice. This is the first study to examine the presence and clonal expansion of specific TCR sequences in obesity and suggest a plausible antigen. CrossRefPubMedPubMedCentral
79.
Xiao L, Yang X, Lin Y, Li S, Jiang J, Qian S, et al. Large adipocytes function as antigen-presenting cells to activate CD4+ T cells via upregulating MHCII in obesity. Int J Obes. 2016;40:112–20.CrossRef
80.
Morris DL, Cho KW, Delproposto JL, Oatmen KE, Geletka LM, Martinez-Santibanez G, et al. Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes. 2013;62:2762–72.CrossRefPubMedPubMedCentral
81.
Deng T, Liu J, Deng Y, Minze L, Xiao X, Wright V, et al. Adipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells. Nature Comm. 2017;8:15725.CrossRef
82.
Seijkens T, Kusters P, Chatzigeorgiou A, Chavakis T, Lutgens E. Immune cell crosstalk in obesity: a key role for costimulation? Diabetes. 2014;63:3982–91.CrossRefPubMed
83.
Chatzigeorgiou A, Seijkens T, Zarzycka B, Engel D, Poggi M, van den Berg S, et al. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. PNAS. 2014;111:2686–91.CrossRefPubMedPubMedCentral
84.
• Romano M, Fanelli G, Tan N, Nova-Lamperti E, McGregor R, Lechler RI, et al. Expanded regulatory T cells induce alternatively activated monocytes with a reduced capacity to expand T helper-17 cells. Front Immunol. 2018;9:1625 This study showed that expanded Tregs promote M2 polarization more efficiently than freshly isolated Tregs. Expanded Tregs suppressed monocyte NF-κB activation, IL-6 and TNF production, co-stimulatory and MHC-class II expression, and Th17 expansion. Expanded Tregs also increased CD206 and heme oxygenase-1 expression, and IL-10 production. This was the first study to identify the mechanism by which expanded Tregs suppress autoimmunity and transplant rejection. CrossRefPubMedPubMedCentral
85.
Safinia N, Vaikunthanathan T, Fraser H, Thirkell S, Lowe K, Blackmore L, et al. Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation. Oncotarget. 2016;7:7563–77.CrossRefPubMedPubMedCentral
86.
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Fat Treg cells: a liaison between the immune and metabolic systems. Nat Med. 2009;15:930–9.CrossRefPubMedPubMedCentral
87.
Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486:549–53.CrossRefPubMedPubMedCentral
88.
Raghuraman S, Donkin I, Versteyhe S, Barrès R, Simar D. The emerging role of epigenetics in inflammation and immunometabolism. Trends Endocrinol Metab. 2016;27:782–95.CrossRefPubMed
89.
Schoenborn JR, Dorschner MO, Sekimata M, Santer DM, Shnyreva M, Fitzpatrick DR, et al. Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-gamma. Nat Immunol. 2007;8:732–42.CrossRefPubMedPubMedCentral
90.
Saeed S, Quintin J, Kerstens HHD, Rao NA, Aghajanirefah A, Matarese F, et al. Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity. Science. 2014;345:1251086.CrossRefPubMedPubMedCentral
91.
Takeuch O, Akira S. Epigenetic control of macrophage polarization. Eur J Immunol. 2011;41:2490–3.CrossRefPubMed
92.
Sun L, Marin De Evsikova C, Bian K, Achille A, Telles E, Seto E. HDAC11 deficiency prevents high-fat diet-induced obesity and metabolic syndrome. bioRxiv. 2018.
93.
Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. Sirt1 protects against high-fat diet-induced metabolic damage. PNAS. 2008;105:9793–8.CrossRefPubMedPubMedCentral
94.
Schug TT, Xu Q, Gao H, Peres-da-Silva A, Draper DW, Fessler MB, et al. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol. 2010;30:4712–21.CrossRefPubMedPubMedCentral
95.
Jiang S, Zhang L-F, Zhang H-W, Hu S, Lu M-H, Liang S, et al. A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 2012;31:1985–98.CrossRefPubMedPubMedCentral
96.
Kim S, Lee E, Jung J, Lee JW, Kim HJ, Kim J, et al. microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene. 2018;37:2982.CrossRefPubMedPubMedCentral
97.
Huffaker TB, O’Connell RM. miR-155-SOCS1 as a functional axis: satisfying the burden of proof. Immunity. 2015;43:3–4.CrossRefPubMed
98.
Gaudet AD, Fonken LK, Gushchina LV, Aubrecht TG, Maurya SK, Periasamy M, et al. miR-155 deletion in female mice prevents diet-induced obesity. Sci Rep. 2016;6:22862.CrossRefPubMedPubMedCentral
99.
Velázquez KT, Enos RT, Carson MS, Cranford TL, Bader JE, Sougiannis AT, et al. miR155 deficiency aggravates high-fat diet-induced adipose tissue fibrosis in male mice. Physiol Rep. 2017;5:e13412.CrossRefPubMedPubMedCentral
100.
Pan Y, Hui X, Hoo RLC, Ye D, Chan CYC, Feng T, et al. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J Clin Invest. 2019;129:834–49.CrossRefPubMedPubMedCentral
Metadaten
Titel
Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity
verfasst von
Heather L. Caslin
Alyssa H. Hasty
Publikationsdatum
27.03.2019
Verlag
Springer US
Erschienen in
Current Obesity Reports / Ausgabe 3/2019
Elektronische ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-019-00344-2

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Bewegungs-, Dehnungs- und Entspannungsübungen im Wasser lindern die Beschwerden von Patientinnen mit Fibromyalgie besser als das Üben auf trockenem Land. Das geht aus einer spanisch-brasilianischen Vergleichsstudie hervor.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

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.

VHF-Ablation nützt wohl nur bei reduzierter Auswurfleistung

02.05.2024 Ablationstherapie Nachrichten

Ob die Katheterablation von Vorhofflimmern bei Patienten mit Herzinsuffizienz die Komplikationsraten senkt, scheint davon abzuhängen, ob die Auswurfleistung erhalten ist oder nicht. Das legen die Ergebnisse einer Metaanalyse nahe.

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