The Role of PGC-1alpha in Adipocyte Differentiation and Fat Mobilization

Abstract

Calorie Restriction (CR) without malnutrition extends mean and maximal lifespan in multiple species, although the mechanism is unknown. CR has a dramatic effect on adipose tissue morphology, gene expression and energy metabolism. The concept of adipose tissue as an endocrine organ has come into focus recently, raising the possibility that the whole-body beneficial effects of CR are initiated in adipose tissue. Transcription co-activator PGC-1alpha is a key regulator of energy metabolism. CR influences components of the PGC-1alpha pathway, resulting in PGC-1alpha activation in adipose tissue. We set out to determine whether PGC-1alpha plays a role in the regulation of adipocyte function. Here we show the effect of manipulation of PGC-1alpha activity on two parameters of adipocyte function; differentiation and fat mobilization. First, we show that pharmacological inhibition of PGC-1? pathway accelerates differentiation, and activation of PGC-1alpha pathway impairs differentiation. Second, pharmacological activation of PGC-1alpha in mature adipocytes increases fat mobilization. Third, genetically increased levels of PGC-1alpha also inhibit differentiation and fat storage. This study demonstrates that PGC-1alpha plays a role in the processes of differentiation and fat mobilization in cultured adipocytes. These data are consistent with involvement of PGC-1alpha in the mechanism of adipose remodeling induced by CR.