Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi


CiteScore 2018: 2.43

SCImago Journal Rank (SJR) 2018: 0.947
Source Normalized Impact per Paper (SNIP) 2018: 0.837

Online
ISSN
1868-1891
See all formats and pricing
More options …
Volume 33, Issue 1

Issues

Subcutaneous adipose tissue biology in metabolic syndrome

Ishwarlal Jialal
  • Corresponding author
  • Section of Endocrinology, VA Medical Center, Mather and California North-State University College of Medicine, 9700 West Taron Drive, Elk Grove, CA 95757, USA, Fax: +916-686-7310
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sridevi Devaraj
  • Department of Pathology and Immunology, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-01-20 | DOI: https://doi.org/10.1515/hmbci-2017-0074

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.

Keywords: adipokines; inflammation; insulin resistance; macrophages; metabolic syndrome; subcutaneous adipose tissue

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.Web of ScienceGoogle Scholar

  • [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.Google Scholar

  • [3]

    Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes. 2013;2013:393192.PubMedGoogle Scholar

  • [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.PubMedCrossrefGoogle Scholar

  • [5]

    Jialal I, Devaraj S, Rajamani U. Dysregulation of monocyte biology in metabolic syndrome. Expert Rev Endocrinol Metab. 2014;9:213–21.CrossrefGoogle Scholar

  • [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.Web of SciencePubMedCrossrefGoogle Scholar

  • [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.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [8]

    Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia. 2012;55:2319–26.Web of ScienceCrossrefPubMedGoogle Scholar

  • [9]

    Yamauchi T, Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab. 2013;17:185–96.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [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.PubMedCrossrefGoogle Scholar

  • [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.Web of SciencePubMedCrossrefGoogle Scholar

  • [13]

    La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4:371–9.CrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [17]

    King VL, Thompson J, Tannock LR. Serum amyloid A in atherosclerosis. Curr Opin Lipidol. 2011;22:302–7.PubMedCrossrefGoogle Scholar

  • [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.CrossrefWeb of SciencePubMedGoogle Scholar

  • [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.Web of ScienceGoogle Scholar

  • [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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.CrossrefWeb of ScienceGoogle Scholar

  • [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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [23]

    Tan BK, Adya R, Randeva HS. Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med. 2010;20:143–8.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [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.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [29]

    Schumann RR. Old and new findings on lipopolysaccharide-binding protein: a soluble pattern-recognition molecule. Biochem Soc Trans. 2011;39:989–93.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [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.CrossrefWeb of SciencePubMedGoogle Scholar

  • [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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [32]

    Stefan N, Haring HU. The role of hepatokines in metabolism. Nat Rev Endocrinol. 2013;9:144–52.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.Web of SciencePubMedCrossrefGoogle Scholar

  • [36]

    DiSpirito JR, Mathis D. Immunological contributions to adipose tissue homeostasis. Semin Immunol. 2015;27:315–21.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [38]

    Jialal I, Rajamani U. Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metab Syndr Relat Disord. 2014;12:454–6.Web of ScienceCrossrefPubMedGoogle Scholar

About the article

Received: 2017-10-30

Accepted: 2017-11-30

Published Online: 2018-01-20


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.


Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 33, Issue 1, 20170074, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2017-0074.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Purnima Gurung, Karine Moussa, Beverley Adams-Huet, Sridevi Devaraj, and Ishwarlal Jialal
American Journal of Physiology-Endocrinology and Metabolism, 2019, Volume 316, Number 3, Page E504
[2]
Huan Wang, Peng-Fei Xu, Jing-Yi Li, Xue-Jing Liu, Xiao-Yue Wu, Fang Xu, Bei-Chen Xie, Xiao-Min Huang, Zi-Hao Zhou, Abudurexiti Kayoumu, George Liu, and Wei Huang
American Journal of Physiology-Endocrinology and Metabolism, 2019, Volume 316, Number 1, Page E54
[3]
Adeline Divoux, Katalin Sandor, Dora Bojcsuk, Amlan Talukder, Xiaoman Li, Balint L. Balint, Timothy F. Osborne, and Steven R. Smith
Clinical Epigenetics, 2018, Volume 10, Number 1
[4]
Namya Mellouk, Christelle Ramé, Joël Delaveau, Christophe Rat, Eric Maurer, Pascal Froment, and Joëlle Dupont
General and Comparative Endocrinology, 2018
[5]
Yingmei Zhang, Adam T. Whaley-Connell, James R. Sowers, and Jun Ren
Pharmacology & Therapeutics, 2018

Comments (0)

Please log in or register to comment.
Log in