Role of BSCL2 in adipose biology and lipodystrophy

Mutations in Bscl2 have been linked to Congenital Generalized Lipodystrophy type 2 associated with insulin resistance, early onset diabetes and various metabolic derangements, but little is known about its physiological and molecular functions. We and others have demonstrated that BSCL2 plays a key role in adipocyte differentiation and/or lipid droplet formation and maintenance in vitro. This proposed research will focus on identifying the molecular mechanisms of how Bscl2 deficiency leads to adipose tissue loss as well as its implications on whole body energy homeostasis. The proposed experiments will entail the characterization of global Bscl2 deficient mice as well as an assortment of biochemical, molecular and cellular techniques to identify the molecular functions of Bscl2 both in vivo and in vitro. The specific aims include: 1) To elucidate the physiological role of Bscl2 in vivo by use of Bscl2 global deficient mice. 2) To identify the molecular function of Bscl2 in adipose biology by in vitro molecular studies. This will be the first detailed functional analysis of Bscl2 that could shed new light on our understanding of the pathophysiology of adipose tissue loss and its implications on diabetes, metabolism and cardiovascular diseases (AHA Program: Beginning Grant-in-Aid)