Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha.

OBJECTIVE: Adiponectin mRNA expression in isolated subcutaneous and omental adipocytes was examined across a wide range of adiposity to determine whether adiponectin synthesis is impaired in these adipose tissue depots in obese humans. Tumor necrosis factor (TNF)alpha and dexamethasone were tested for inhibitory effects on adiponectin release from human adipocytes in vitro. RESEARCH METHODS AND PROCEDURES: Adipocytes were isolated by collagenase digestion of abdominal adipose tissue obtained from subjects undergoing surgical procedures or outpatient needle biopsy. Adiponectin and leptin mRNA were quantitated by real-time reverse transcriptase-polymerase chain reaction. Adiponectin and leptin secretion from isolated adipocytes treated with dexamethasone or TNFalpha were determined by radioimmunoassay. RESULTS: There was a significant negative correlation between adiponectin gene expression and BMI in subcutaneous adipocytes from 32 women (r = 0.420; p = 0.02). Adiponectin mRNA was also significantly correlated with serum adiponectin (r = 0.44; p = 0.03; n = 25). There was no correlation between adiponectin mRNA expression and BMI in omental adipocytes from 29 women. Leptin mRNA was significantly and positively correlated (r = 0.484; p = 0.01) with BMI in the same omental adipocyte mRNA preparations. In subcutaneous adipocytes from lean subjects, TNFalpha inhibited adiponectin release by 7.4 +/- 1.2% (n = 9, p < 0.05) but had no effect on adiponectin release from subcutaneous or omental adipocytes from obese subjects. Dexamethasone significantly inhibited adiponectin release with 24 hours of treatment. DISCUSSION: The data suggest that reduced adiponectin synthesis in subcutaneous adipocytes contributes to lower serum adiponectin levels in obesity and that glucocorticoids regulate adiponectin gene expression in human adipocytes. TNFalpha does not seem to directly inhibit adiponectin synthesis in human adipocytes.