CIDE family proteins can induce apoptosis when over-expressed in mammalian cells. Three Cide family proteins (Cidea, Cideb and FSP27) were identified in mice. Previous studies using Cidea knockout mice as a model system suggest that Cidea plays an important role in controlling energy homeostasis and lipid metabolism. Cidea-null mice showed higher whole body metabolism and increased lipolysis in brown adipose tissue (BAT). Interestingly, Cidea-null mice were lean with enhanced glucose disposal and resistance to high-fat-diet induced obesity and diabetes. Cidea represents the first protein known in BAT to possibly modulated thermogenesis and lipid metabolism and contribute to the development of obesity and diabetes....[ Read more ]

CIDE family proteins can induce apoptosis when over-expressed in mammalian cells. Three Cide family proteins (Cidea, Cideb and FSP27) were identified in mice. Previous studies using Cidea knockout mice as a model system suggest that Cidea plays an important role in controlling energy homeostasis and lipid metabolism. Cidea-null mice showed higher whole body metabolism and increased lipolysis in brown adipose tissue (BAT). Interestingly, Cidea-null mice were lean with enhanced glucose disposal and resistance to high-fat-diet induced obesity and diabetes. Cidea represents the first protein known in BAT to possibly modulated thermogenesis and lipid metabolism and contribute to the development of obesity and diabetes.

Cideb, which shares sequence homology with Cidea, was shown to be highly expressed in liver, an important organ for lipid and glucose metabolism. The objective of this project is to investigate the physiological role of Cideb protein. To achieve this aim, the targeted gene-disruption animal models for Cideb were generated. Detailed biochemical and physiological analyses were carried out in Cideb-null mice under different feeding conditions. We showed that Cideb-deficient mice are resistant to high-fat diet-induced obesity, hyperlipidemia or liver steatosis. In addition, Cideb-null mice contain lower levels of plasma insulin, and exhibit enhanced hepatic insulin sensitivity. Furthermore, the mutant mice displayed increased fatty acid oxidation but significantly reduced rates of fatty acid biosynthesis. Surprisingly, levels of plasma cholesterol and the rate of cholesterol biosynthesis were also dramatically reduced in these mice. Consistent with the decrease of biosynthesis of fatty acid and cholesterol, expression of key enzymes for the fatty acid and cholesterol biosynthesis pathways in Cideb-null mice was reduced. Taken together, the data have demonstrated that Cideb is a novel important regulator in the pathways of fatty acid and cholesterol biosynthesis, as well as in fatty acid oxidation. Our findings further suggest that Cideb may represent a new therapeutic target for the treatment of metabolic diseases such as obesity, diabetes, liver steatosis, and hypertension.