Inositol Polyphosphate Multikinase in Adipocytes Is Dispensable for Regulating Energy Metabolism and Whole Body Metabolic Homeostasis

Abstract

Adipose tissue plays a central role in regulating whole body energy and glucose homeostasis at both organ and systemic levels. Inositol polyphosphates, such as 5-diphosphoinositol pentakisphosphate, reportedly control adipocyte functions and energy expenditure. However, the physiological roles of the inositol polyphosphate (IP) pathway in the adipose tissue are not yet fully defined. The aim of the present study was to test the hypothesis that inositol polyphosphate multikinase (IPMK), a key enzyme in the IP metabolism, plays a critical role in adipose tissue biology and obesity. We generated adipocyte-specific IPMK knockout ( Ipmk AKO) mice and evaluated metabolic phenotypes by measuring fat accumulation, glucose homeostasis, and insulin sensitivity in adult mice fed either a regular-chow diet or high-fat diet (HFD). Despite substantial reduction of IPMK, Ipmk AKO mice exhibited normal glucose tolerance and insulin sensitivity and did not show changes in fat accumulation in response to HFD-feeding. In addition, loss of IPMK had no major impact on thermogenic processes in response to cold exposure. Collectively, these findings suggest that adipocyte IPMK is dispensable for normal adipose tissue and its physiological functions in whole body metabolism, suggesting the complex roles that inositol polyphosphate metabolism has in the regulation of adipose tissue.