Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes.
Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by hyperinsulinemic-euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase-PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein (MIP), interleukin-8 (IL-8)). Fasting glucose related to VAT expression of TNFalpha, MIP, serum amyloid A (SAA), IL-1alpha, IL-1beta, IL-8, and IL-8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element-binding protein (CREBP), IL-1beta, and IL-8. Insulin action related inversely to VAT complement C3 expression only. There were depot-specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol-binding protein-4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.
Samaras
Katherine
K
[1] Department of Endocrinology, St Vincent's Hospital, Darlinghurst, New South Wales, Australia [2] Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Botelho
Natalia K
NK
Chisholm
Donald J
DJ
Lord
Reginald V
RV
D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D050151:Subcutaneous Fat / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055105:Waist Circumference
D054392:Adipokines; D054405:Chemokine CCL3; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha