Effect of secretin on preadipocyte, differentiating and mature adipocyte functions

Abstract

Several gastrointestinal peptides are now recognized to have target functions beyond the intestinal wall, including effects on adipocytes. Secretin (SEC), one of the first identified, has not been evaluated in this context. Using cultured 3T3-L1 preadipocytes, adipocytes and primary rat adipocytes we evaluated the effect of SEC on cell proliferation, mitochondrial activity, differentiation, triglyceride (TG) synthesis, lipolysis as well expression of the SEC receptor (SCTR) in rodent and human adipose tissues. In preadipocytes, SEC significantly increased mitochondrial activity (115%; P<0.01), thymidine incorporation (149.7%; P<0.05) and C/EBPβ expression (123.4%; P<0.05). During standard differentiation, SCTR mRNA increased up to a maximum of ninefold (P<0.001). In human adipose tissue, SCTR correlated with body mass index and plasma insulin, and SCTR mRNA expression was also detected in rat adipose tissues. SEC supplementation during differentiation enhanced TG accumulation (+138%; P<0.01). In mature adipocytes, SEC increased fatty acid (FA) uptake (186%; P<0.01), adiponectin and monocyte chemotactic protein-1 secretion (+142% and +149%, respectively; P<0.05) and mRNA expression of PPARγ (+206%; P<0.01), FABP4 (+164%; P<0.001), DGAT-1 (+144%; P<0.01), adiponectin (+138%; P<0.001) and CD36 (+149%; P<0.05). In primary rat adipocytes, SEC also increased FA uptake (137%; P<0.05). Pretreatment with a SEC antagonist impaired SEC-induced FA uptake and cAMP accumulation. SEC treatment simultaneously stimulated lipolysis measured as glycerol release in 3T3-L1 adipocytes and rat adipose tissue. The present results suggest that SEC is a potent modulator of adipocyte functions, demonstrating overall a role in enhanced substrate cycling.