Physiological roles of CIDEs: CIDEA deficient mice exhibit lean phenotype and are obesity resistant

Abstract

The thermogenic activity of brown adipose tissue (BAT), important for adaptive thermogenesis and energy expenditure, is mediated by the mitochondrial uncoupling protein-1 (UCP1) that uncouples ATP generation and dissipates the energy as heat. It was show here that Cidea, a functionally unknown protein sharing sequence similarity with the N-terminal region of DNA fragmentation factors DFF40/45, is expressed at high levels in BAT. Cidea null mice exhibited higher metabolic rate, increased lipolysis in BAT and higher core body temperature when subjected to cold treatment. Most strikingly, Cidea null mice are lean and resistant to diet-induced obesity and diabetes. Furthermore, evidence is provided that the role of Cidea in regulating thermogenesis, lipolysis and obesity, may be mediated in part through its direct suppression of UCP1 activity. The data thus demonstrate a novel role for Cidea in regulating energy balance and adiposity.