Adipose Tissue Dysregulation in Patients with Metabolic Syndrome

Andrew A.Bremer,*Sridevi Devaraj,*Alaa Afify,and Ishwarlal Jialal

Department of Pediatrics(A.A.B.),Vanderbilt University,Nashville,Tennessee37232;Laboratory for Atherosclerosis and Metabolic Research(S.D.,A.A.,I.J.)and Clinical and Translational Science Center (S.D.,I.J.),University of California,Davis,Medical Center,Sacramento,California95817;and Veterans Affairs Medical Center(S.D.,A.A.,I.J.),Sacramento,California95655

Context:The metabolic syndrome(MetS)is associated with increased risk of diabetes and cardio-vascular disease(CVD).Numerous groups have shown increased circulating biomarkers of inflam-mation in MetS.However,there are scanty data on the cellular sources contributing to this low-grade inflammation.

Objective:The aim of this study was to determine the role of sc adipose tissue(SAT)biology in nascent MetS without concomitant diabetes or CVD.

Patients and Methods:Subjects with MetS and controls were recruited after informed consent. Fasting blood was collected,and SAT was obtained by biopsy.

Results:Circulating biomarkers of inflammation and insulin resistance,high-sensitivity C-reactive protein(hsCRP),IL-6,IL-1?,leptin,serum amyloid A,and retinol-binding protein-4(RBP-4)con-centrations were significantly higher in the MetS subjects than controls,whereas adiponectin concentrations were lower.In SAT,leptin,RBP-4,CRP,serum amyloid A,plasminogen activator inhibitor-1,IL-1,IL-6,IL-8,and monocyte chemotactic protein-1(MCP-1)levels were significantly higher in MetS than controls.These differences except for RBP-4persisted after adjusting for waist circumference.In addition,there were significantly increased numbers of macrophages infiltrating the SAT of MetS and increased numbers of crown-like structures compared with controls.hsCRP correlated positively with homeostasis model assessment and SAT MCP-1and negatively with adiponectin.Homeostasis model assessment correlated positively with plasminogen activator in-hibitor-1,RBP-4,and SAT MCP-1.

Conclusions:We make the novel observation that SAT of MetS has increased macrophage recruit-ment with cardinal crown-like structure features and contributes to the increased cellular inflam-mation that produces increased levels of biomarkers that are correlated with both insulin resistance and low-grade inflammation.These aberrations could contribute to the progression of MetS and the increased risk for diabetes and CVD.(J Clin Endocrinol Metab96:E1782–E1788,2011)

T he metabolic syndrome(MetS)comprises a cluster of cardiometabolic risk markers with insulin resistance and adiposity as central features(1–4).Five diagnostic criteria for MetS have been identified[central obesity,dys-lipidemia,high triglycerides(TG)and/or low high-density lipoprotein cholesterol(HDL-C),hypertension,and im-paired fasting glucose]by the Adult Treatment Panel III criteria of the National Cholesterol and Education Pro-gram,and the presence of three features is considered suf-ficient to diagnose the syndrome(2,4,5).Using this def-

ISSN Print0021-972X ISSN Online1945-7197

Printed in U.S.A.

Copyright?2011by The Endocrine Society

doi:10.1210/jc.2011-1577Received May23,2011.Accepted August1,2011. First Published Online August24,2011*A.A.B.and S.D.made equal contributions.

Abbreviations:BP,Blood pressure;CAD,coronary artery disease;CLS,crown-like structures; CVD,cardiovascular disease;HDL-C,high-density lipoprotein cholesterol;HOMA,homeostasis model assessment;hpf,high-power field;hsCRP,high-sensitivity C-reactive protein;MCP-1, monocyte chemotactic protein-1;MetS,metabolic syndrome;PAI-1,plasminogen activator inhibitor-1;RBP-4,retinol-binding protein-4;SAA,serum amyloid A;SAT,sc adipose tissue;TG, triglycerides;VAT,visceral adipose tissue;WC,waist circumference.

J C E M O N L I N E

H o t T o p i c s i n T r a n s l a t i o n a l E n d o c r i n o l o g y—E n d o c r i n e R e s e a r c h http://www.doczj.com/doc/9733bbd3a300a6c30d229f2e.html J Clin Endocrinol Metab,November2011,96(11):E1782–E1788