In vitro and in vivo effects of metformin on human adipose tissue adiponectin

Objective: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin. Methods: For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups. Results: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group. Conclusion: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.