Subcutaneous adipose tissue biology in metabolic syndrome
-
Ishwarlal Jialal
und
Sridevi Devaraj
Abstract
Metabolic syndrome (MetS) is a common global problem that comprises the cardio-metabolic cluster and predisposes to both diabetes and cardiovascular diseases. Although the pathogenic mechanisms have not been elucidated, both increased inflammation and insulin resistance play a pivotal role. It appears that both monocyte/macrophages and adipose tissue (AT) conspire to accentuate both the pro-inflammatory state and increased insulin resistance. Whilst there are scant data on visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) biology, there are data on subcutaneous adipose tissue (SAT) dysregulation. There is a significant increase in macrophages and crown-like structures in the SAT of patients with MetS. With respect to adipokines, there is an increase in plasma leptin, plasminogen activator inhibitor-1, retinol-binding protein-4 (RBP-4), chemerin, serum amyloid-A, C-reactive protein (CRP), interleukin-1, -6, -8, lipopolysaccharide, fetuin A (FetA) and a decrease in adiponectin and omentin-1. All of the abnormalities in plasma were also confirmed for SAT-secreted adipokines except for adiponectin and RBP-4 which derive largely from VAT. As many of these biomediators correlate with both insulin resistance and increased inflammation, we can posit that dysregulation of SAT is detrimental and contributes to both the pathogenesis of MetS and its sequalae. Furthermore, as future directions, much work is needed with respect to VAT/EAT biology, autophagy, sirtuins, the gut microbiome, browning of AT, to further elucidate this common syndrome and identify potential therapeutic targets to forestall its serious complications.
Acknowledgements
We thank Jeanita Jialal, BA for manuscript preparation and proofing of final submission.
Author Statement
Research funding: Authors state no funding involved.
Conflict of interest: Authors state no conflict of interest.
Informed consent: Informed consent is not applicable.
Ethical approval: The conducted research is not related to either human or animals use.
References
[1] Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. International Diabetes Federation Task Force on Epidemiology and Prevention: National Heart, Lung and Blood Institute: American Heart Association: World Heart Federation: International Atherosclerosis Society: International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Circulation. 2009;120:1640–5.10.1161/CIRCULATIONAHA.109.192644Suche in Google Scholar PubMed
[2] Lam DW, LeRoith D. Metabolic syndrome. In: De Groot LJ, Chrousos G, Dungan K, editor(s).Endotext. South Dartmouth, MA: MDText.com, 2015:1–34.Suche in Google Scholar
[3] Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes. 2013;2013:393192.10.1155/2013/393192Suche in Google Scholar PubMed PubMed Central
[4] Devaraj S, Rosenson RS, Jialal I. Metabolic syndrome: an appraisal of the pro-inflammatory and procoagulant status. Endocrinol Metab Clin North Am. 2004;33:431–53.10.1016/j.ecl.2004.03.008Suche in Google Scholar PubMed
[5] Jialal I, Devaraj S, Rajamani U. Dysregulation of monocyte biology in metabolic syndrome. Expert Rev Endocrinol Metab. 2014;9:213–21.10.1586/17446651.2014.890046Suche in Google Scholar PubMed
[6] Adams-Huet B, Devaraj S, Siegel D, Jialal I. Increased adipose tissue insulin resistance in metabolic syndrome: relationship to circulating adipokines. Metab Syndr Relat Disord. 2014;12:503–7.10.1089/met.2014.0092Suche in Google Scholar PubMed
[7] Jialal I, Huet BA, Kaur H, Chien A, Devaraj S. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care. 2012;35:900–4.10.2337/dc11-2375Suche in Google Scholar PubMed PubMed Central
[8] Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012;55:2319–26.10.1007/s00125-012-2598-xSuche in Google Scholar PubMed
[9] Yamauchi T, Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab. 2013;17:185–96.10.1016/j.cmet.2013.01.001Suche in Google Scholar PubMed
[10] Frystyk J, Berne C, Berglund L, Jensevik K, Flyvbjerg A, Zethelius B. Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men. J Clin Endocrinol Metab. 2007;92:571–6.10.1210/jc.2006-1067Suche in Google Scholar PubMed
[11] Nilsson PM, Engström G, Hedblad B, Frystyk J, Persson MM, Berglund G, et al. Plasma adiponectin levels in relation to carotid intima media thickness and markers of insulin resistance. Arterioscler Thromb Vasc Biol. 2006;26:2758–62.10.1161/01.ATV.0000249638.01416.4bSuche in Google Scholar PubMed
[12] Devaraj S, Swarbrick MM, Singh U, Adams-Huet B, Havel PJ, Jialal I. CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers. Am J Clin Pathol. 2008;129:815–22.10.1309/RN84K51B2JJY1Y0BSuche in Google Scholar PubMed PubMed Central
[13] La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4:371–9.10.1038/nri1350Suche in Google Scholar PubMed
[14] Dyck DJ, Heigenhauser GJ, Bruce CR. The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol (Oxf). 2006;186:5–16.10.1111/j.1748-1716.2005.01502.xSuche in Google Scholar PubMed
[15] Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897–901.10.1038/29795Suche in Google Scholar PubMed
[16] Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, et al. Placma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation. 2001;104:3052–6.10.1161/hc5001.101061Suche in Google Scholar PubMed
[17] King VL, Thompson J, Tannock LR. Serum amyloid A in atherosclerosis. Curr Opin Lipidol. 2011;22:302–7.10.1097/MOL.0b013e3283488c39Suche in Google Scholar PubMed
[18] Antuan-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008;34:2–11.10.1016/j.diabet.2007.09.004Suche in Google Scholar PubMed
[19] Bremer AA, Devaraj S, Afify A, Jialal I. Adipose tissue dysregulation in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011;91:E1782–8.10.1210/jc.2011-1577Suche in Google Scholar PubMed PubMed Central
[20] Piya MK, Mc Ternan PG, Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol. 2013;216:T1–15.10.1530/JOE-12-0498Suche in Google Scholar PubMed
[21] Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, et al. Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population. J Clin Endocrinol Metab. 2009;94:3085–8.10.1210/jc.2008-1833Suche in Google Scholar PubMed PubMed Central
[22] Jialal I, Devaraj S, Kaur H, Adams-Huet B, Bremer AA. Increased chemerin and decreased omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metab. 2013;98:E514–7.10.1210/jc.2012-3673Suche in Google Scholar PubMed
[23] Tan BK, Adya R, Randeva HS. Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med. 2010;20:143–8.10.1016/j.tcm.2010.12.002Suche in Google Scholar PubMed
[24] De Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Ndubuizu K, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes. 2007;56:1655–61.10.2337/db06-1506Suche in Google Scholar PubMed
[25] Katsi V, Vamvakou G, Lekakis J, Tousoulis D, Stefanadis C, Makris T, et al. Omentin, fat and heart: classical music with new instruments. Heart Lung Circ. 2014;23:802–6.10.1016/j.hlc.2014.03.013Suche in Google Scholar PubMed
[26] Shang FJ, Wang JP, Lie XT, Zheng QS, Xue YS, Wang B, et al. Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome. Biomarkers. 2011;16:657–62.10.3109/1354750X.2011.622789Suche in Google Scholar PubMed
[27] Luna-Luna M, Medina-Urrutia A, Vargas-Alarcón V, Coss-Rovirosa F, Vargas-Barrón J, Perez-Mendez O. Adipose tissue in metabolic syndrome: onset and progression of atherosclerosis. Arch Med Res. 2015;46:392–407.10.1016/j.arcmed.2015.05.007Suche in Google Scholar PubMed
[28] Norata GD, Ongari M, Garlaschelli K, Raselli S, Grigore L, Catapano AL. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur J Endocrinol. 2007;156:279–84.10.1530/eje.1.02338Suche in Google Scholar PubMed
[29] Schumann RR. Old and new findings on lipopolysaccharide-binding protein: a soluble pattern-recognition molecule. Biochem Soc Trans. 2011;39:989–93.10.1042/BST0390989Suche in Google Scholar PubMed
[30] Jialal I, Devaraj S, Bettaieb A, Haj F, Adams-Huet B. Increased adipose tissue secretion of fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome. Atherosclerosis. 2015;241:130–7.10.1016/j.atherosclerosis.2015.04.814Suche in Google Scholar PubMed
[31] Moreno-Navaratte JM, Escote X, Ortega F, Serino M, Campbell M, Michalski MC, et al. A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation and obesity associated adipose tissue dysfunction. Diabetologia. 2013;56:2524–37.10.1007/s00125-013-3015-9Suche in Google Scholar PubMed
[32] Stefan N, Haring HU. The role of hepatokines in metabolism. Nat Rev Endocrinol. 2013;9:144–52.10.1038/nrendo.2012.258Suche in Google Scholar PubMed
[33] Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S, et al. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem. 2013;288:28324–30.10.1074/jbc.C113.495473Suche in Google Scholar PubMed PubMed Central
[34] Jialal I, Adams-Huet B, Devaraj S. Factors that promote macrophage homing to adipose tissue in metabolic syndrome. J Diabetes Complications. 2016;30:1434–6.10.1016/j.jdiacomp.2016.07.031Suche in Google Scholar PubMed
[35] Jialal I, Adams-Huet B, Major A, Devaraj S. Increased fibrosis and angiogenesis in subcutaneous gluteal adipose tissue in nascent metabolic syndrome. Diabetes Metab. 2017;43:364–7.10.1016/j.diabet.2016.12.004Suche in Google Scholar PubMed
[36] DiSpirito JR, Mathis D. Immunological contributions to adipose tissue homeostasis. Semin Immunol. 2015;27:315–21.10.1016/j.smim.2015.10.005Suche in Google Scholar PubMed PubMed Central
[37] Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte. FASEB J. 2017;31:4240–55.10.1096/fj.201601125RRRSuche in Google Scholar PubMed
[38] Jialal I, Rajamani U. Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 2014;12:454–6.10.1089/met.2014.1504Suche in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Review Articles
- Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk
- Visceral adipose tissue in patients with severe mental illness
- Mini Review Articles
- Subcutaneous adipose tissue biology in metabolic syndrome
- The origin and purpose of layers of subcutaneous adipose tissue in pigs and man
- Original Article
- Lipedema: friend and foe
Artikel in diesem Heft
- Review Articles
- Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk
- Visceral adipose tissue in patients with severe mental illness
- Mini Review Articles
- Subcutaneous adipose tissue biology in metabolic syndrome
- The origin and purpose of layers of subcutaneous adipose tissue in pigs and man
- Original Article
- Lipedema: friend and foe
