Obestatin inhibits lipogenesis and glucose uptake in isolated primary rat adipocytes.

Ghrelin and obestatin are encoded by the preproghrelin gene and originate from post-translational processing of the preproghrelin peptide. Obestatin is mainly present in the stomach, but its action is focused on appetite inhibition in opposition to ghrelin function. Recently, it has been presented that obestatin may regulate adipocyte metabolism and influence fat content. However, obestatin action is still poorly understood. Therefore, we aimed to investigate obestatin function on adipocyte metabolism in the rat. We studied changes in the mRNA expression of active and inactive isoforms of obestatin receptors. In addition, we analyzed influence of obestatin on lipogenesis, lipolysis and glucose transport in isolated adipocytes. Moreover, we also performed analysis of obestatin action on lipolysis in differentiated rat preadipocytes with silenced obestatin receptor. We found significantly higher expression of the obestatin receptor Gpr39-1a active form at an mRNA level following adipocytes incubation with obestatin. We did not observe expression changes in the inactive form of obestatin receptor Gpr39-1b. Additionally, we found significant changes in Gpr39-1a expression following obestatin receptor silencing in cells incubated with obestatin in comparison to control. Obestatin inhibited both, basal and insulin-stimulated lipogenesis and glucose transport in adipocytes. Furthermore, obestatin potentiated adrenalin-stimulated lipolysis. We also found reduced glycerol release following obestatin incubation in adipocytes with silenced Gpr39 gene. Our results indicate that obestatin acts via the GPR39 receptor in isolated adipocytes, and that through this mechanism obestatin influences lipid accumulation, glucose uptake and lipolysis.