Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance.

CONTEXT Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice. Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance. OBJECTIVE The objective of the study was to elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance. DESIGN The design was to quantify STAMP2 in human abdominal sc and omental white adipose tissue (WAT), isolated adipocytes, and stroma and in vitro differentiated preadipocytes and relate levels of STAMP2 in sc WAT to clinical and adipocyte phenotypes involved in insulin resistance. PARTICIPANTS Nonobese and obese women and men (n = 236) recruited from an obesity clinic or through local advertisement. MAIN OUTCOME MEASUREMENT Clinical measures included body mass index, body fat, total adiponectin, and homeostasis model assessment as measure of overall insulin resistance. In adipocytes we determined cell size, sensitivity of lipolysis and lipogenesis to insulin, adiponectin secretion, and inflammatory gene expression. RESULTS STAMP2 levels in sc and visceral WAT and adipocytes were increased in obesity (P = 0.0008-0.05) but not influenced by weight loss. Increased WAT STAMP2 levels associated with a high amount of body fat (P = 0.04), high homeostasis model assessment (P = 0.01), and large adipocytes (P = 0.02). Subjects with high STAMP2 levels displayed reduced sensitivity of adipocyte lipogenesis (P = 0.04) and lipolysis (P = 0.03) to insulin but had normal adiponectin levels. WAT STAMP2 levels correlated with expression of the macrophage marker CD68 (P = 0.0006). CONCLUSION Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin, but the role of STAMP2 in obesity and its complications seems different from that in mice.

[1]  U. Smith,et al.  Culprit Underlying the Metabolic Syndrome and Atherosclerosis , 2007 .

[2]  A. Häkkinen,et al.  Adipose Tissue Inflammation and Increased Ceramide Content Characterize Subjects With High Liver Fat Content Independent of Obesity , 2007, Diabetes.

[3]  Eric Vaillancourt,et al.  Coordinated Regulation of Nutrient and Inflammatory Responses by STAMP2 Is Essential for Metabolic Homeostasis , 2007, Cell.

[4]  P. Arner,et al.  Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α , 2006, Diabetes.

[5]  C. Tomkiewicz,et al.  Expression of macrophage‐selective markers in human and rodent adipocytes , 2005, FEBS letters.

[6]  P. Arner,et al.  Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction , 2005, Diabetologia.

[7]  P. Arner,et al.  Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance. , 2004, The Journal of clinical endocrinology and metabolism.

[8]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[9]  F. Lönnqvist,et al.  Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. , 2002, Diabetes.

[10]  F. Lönnqvist,et al.  Mapping of Early Signaling Events in Tumor Necrosis Factor-α-mediated Lipolysis in Human Fat Cells* , 2002, The Journal of Biological Chemistry.

[11]  C. Klein,et al.  Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion* , 2001, The Journal of Biological Chemistry.

[12]  E. Bonora,et al.  Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , 2000, Diabetes care.