The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.

Context: Aquaporin-7 is required for efflux of glycerol from adipocytes and influences whole-body glucose homeostasis in animal studies. Objective: Our objective was to test the hypothesis that AQP7 gene expression levels may be affected by presence of obesity and type 2 diabetes in humans. Design: The obesity study cohort consisted of 12 lean, 22 nonseverely obese, and 13 severely obese subjects. The type 2 diabetes study cohort consisted of 17 lean and 39 obese type 2 diabetic patients. Circulating levels of plasma soluble proteins monocyte chemoattractant protein-1, TNF receptors 1 and 2, and IL-6 and glycerol were measured. The sc adipose tissue gene expression of AQP7, MCP-1, IL-6, TNFα, PPARγ, and SREBP1c genes was measured by real-time PCR. AQP7 gene mutation analysis was performed. Results: Severely obese women showed lower AQP7 expression levels compared with lean and nonseverely obese (P < 0.001). Moreover, circulating glycerol concentration was lower in severely obese subjects, but no correlation with AQP7 adipose tissue expression was observed. AQP7 expression was negatively related with proinflammatory genes (for monocyte chemoattractant protein-1, r = −0.203 and P = 0.044; for TNFα, r = −0.209 and P = 0.036). Concerning adipogenic factors, AQP7 expression levels were found to be positively determined by PPARγ mRNA expression levels (r = 0.265; P = 0.012). AQP7 expression did not show differences regarding the presence of type 2 diabetes. Conclusion: Expression of AQP7 is down-regulated in women with severe obesity. The expression of this glycerol channel is not affected by type 2 diabetes.