Stimulation of white adipose tissue lipolysis by xenin, a neurotensin-related peptide

Xenin is a gastrointestinal hormone that belongs to the neurotensin family. Central administration of xenin to obese mice reduces food intake and body weight gain and causes alterations in the expression of lipid metabolism-related genes and proteins in white adipose tissue (WAT). However, it has not been tested whether or not xenin directly acts on adipose tissue and alters lipid metabolism. The present study was performed to address this possibility by examining the effect of xenin treatment on the levels of glycerol and free fatty acids (FFA) and expression levels of lipolysis marker proteins ex vivo in cultured mouse WAT. Xenin treatment significantly increased concentrations of glycerol and FFA in culture media and increased phosphorylation of hormone sensitive lipase (HSL) in ex vivo cultured WAT. These findings support the hypothesis that xenin directly acts on adipose tissues and stimulates lipolysis. Thus, enhancement of xenin action and its downstream signaling may offer a novel and effective therapy for obese patients by reducing the amount of stored fat in adipose tissue.