1764-P: Insulin Sensitive Induction of Adipogenesis

Abstract

Healthy adipose tissue has a remarkable ability to adapt to energy intake through contraction and expansion. A large body of evidence pin-points the ability expand adipose tissue as vital to maintain whole body lipid homeostasis and insulin sensitivity in humans as well as in mice. Increases in fat mass can be driven by expansion of existing adipocytes or by recruitment of new adipocytes from adipose tissue pre-courser cells or preadipocytes (Adipogenesis). Failure to expand adipose tissues as well as appearance of dysfunctional large adipocytes both result in local and systemic insulin resistance. Conversely, strategies to preserve adipocyte function during tissue expansion through enhanced adipogenesis could preserve insulin function in the face of obesity or high caloric intake. In order to study the hormonal control of adipose tissue expansion we have examined the ability of insulin and IGF-1 to induce adipogenesis in isolated rodent primary SVF cells. We find that both insulin and IGF-1 dose dependently induce lipid droplet accumulation and expression of adipocyte genes in primary cells isolated from mouse epididymal and subcutaneous adipose depots. Surprisingly, adipogenesis in mouse SVF cells is a very insulin sensitive process and more specifically we identify CD45neg/Ly6c low SVF cells isolated from epididymal fat pads as extremely sensitive to insulin induced adipogenesis. These results indicate that insulin signaling directly in preadipocytes could drive adipocyte differentiation in vivo e.g., during high insulin levels in serum in response to prolonged periods of high caloric intake or lipid induced insulin resistance. Disclosure T.Å. Pedersen: Employee; Spouse/Partner; Cook Medical. Employee; Self; Novo Nordisk A/S. J. Peics: Employee; Self; Novo Nordisk A/S. G.S. Olsen: Employee; Self; Novo Nordisk A/S.