Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

Abstract

To test the hypothesis that depot differences exist for adiponectin, fresh and cultured human VAT and SAT from obese type 2 diabetic (T2D) and obese nondiabetic (ND) subjects was examined to determine whether differences in adiponectin content and secretion occurred as a function of depot studied, diabetic status, and response to thiazolidinedione treatment. VAT and SAT were obtained by biopsy and AT explants cultured in defined media for 7 days. Protein expression was assessed by Western blot. Adiponectin content of conditioned medium was determined by radioimmunoassay. Diabetic status had no effect on adiponectin secretion over days 0 -2 of culture. In ND SAT, secretion fell over days 2-4 but was sustained at greater levels vs. T2D SAT. In both ND and T2D VAT, adiponectin secretion was low, similar to T2D SAT. Over the 7-day culture period, cellular adiponectin increased in ND SAT and VAT; it remained unchanged in T2D SAT and VAT. Pioglitazone increased adiponectin secretion and content in all SAT. Pioglitazone failed to increase adiponectin secretion from either ND or T2D VAT and increased cellular content only in ND VAT. AT depot differences exist in the secretion of adiponectin and responsiveness to thiazolidinedione treatment. These data suggest that SAT, not VAT, appears to be the major contributor to increased circulating adipopnectin levels in response to pioglitazone treatment. adipose tissue physiology; type 2 diabetes mellitus; body fat distribution; thiazolidinediones; leptin ADIPOSE TISSUE (AT) is recognized to play an important role in the regulation of lipid/carbohydrate metabolism, energy homeostasis, and insulin sensitivity (55) via release of metabolically active products that regulate insulin sensitivity and fat metabolism (27). Many AT products exert opposing actions on insulin sensitivity, inflammation, and fatty acid metabolism. For example, AT products IL-6, TNF-␣, and resistin may impair insulin sensitivity, increase circulating free fatty acids, and exert proinflammatory effects, whereas others such as adiponectin exert insulin-sensitizing effects, reduce free fatty acids, and dampen inflammation (28). The metabolic impact of a given AT depot is therefore related to the relative profile or balance of mediator release.AT is distributed to a variety of locations, and in humans contributions of SAT and VAT can be distinguished (reviewed in Ref. 59). Individuals with increased visceral (V)AT are at higher risk of developing the metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease (32, 59) than those with similar amounts of AT as subcutaneous (S)AT (34). Underlying these findings are depot differences in gene and protein expression (36, 37). These findings lend support to the idea that different AT depots are functionally distinct metabolic units.Circulating levels of adiponectin are low in obese and insulin-resistant subjects (62) and are predictive for development of T2D (30). In contrast, adiponectin is high in lean and insulin-sensitive subjects (50). Interestingly, seru...

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue

“…Motoshima et al 11 and Perrini et al 3 reported that the cultured human omental adipocytes secrete more adiponectin than subcutaneous adipocytes and that its secretion is inversely correlated to BMI, whereas the secretion from the subcutaneous cells was unrelated to BMI. Contrary to this, Phillips et al 29 showed lower adiponectin levels secreted by VAT than SAT explants of obese as well as type 2 diabetic people. These inconsistent findings may be attributed to important methodological differences existing among the studies comparing AT explant cultures and adipocyte cultures.…”

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

“…In fact, different protein production or gene expression of many adipocytokines, including adiponectin, was demonstrated in visceral when compared with subcutaneous fat. The results are not unequivocal: lower adiponectin protein and mRNA levels in visceral versus subcutaneous AT were evidenced in several studies (46,47) while opposite results were reported by other authors (48,49). To date, no study on adiponectin isoforms secretion by visceral AT explants has been reported.…”

Acute Hyperinsulinemia Differentially Regulates Interstitial and Circulating Adiponectin Oligomeric Pattern in Lean and Insulin-Resistant, Obese Individuals

“…Nonetheless, the temporal resolution of the technique is of importance to detect a correct trend when changes from baseline levels are ad- dressed (25). Second, although the characterization of interstitial adiponectin in the sc abdominal AT may not reflect the activity of the whole-body fat, different data indicate that this depot exerts a greater influence on circulating adiponectin than the visceral fat (2,34,35,46). Third, the nonreducing SDS-PAGE may be technically challenging to quantify precisely the adiponectin oligomers also because the Alb-LMW is difficult to separate from the other forms (1,9).…”