Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation.
OBJECTIVE
Our previous study suggests that Cidea, a member of Cide family proteins that share sequence homology with the DNA fragmentation factor and are expressed at high levels in brown adipose tissue, plays an important role in the development of obesity. Cideb, another member of Cide family protein, is highly expressed in the liver. We would like to understand the physiological role of Cideb in the regulation of energy expenditure and lipid metabolism.


METHODS
We generated Cideb-null mice by homolog recombination and then fed both wild-type and Cideb-null mice with high-fat diet (58% fat). We then characterized the animals' adiposity index, food intake, whole-body metabolic rate, liver morphology, rate of fatty acid synthesis and oxidation, insulin sensitivity, and gene expression profile.


RESULTS
Cideb-null mice had lower levels of plasma triglycerides and free fatty acids and were resistant to high-fat diet-induced obesity and live steatosis. In addition, Cideb mutant mice displayed significantly increased insulin sensitivity and enhanced rate of whole-body metabolism and hepatic fatty acid oxidation. More importantly, Cideb-null mice showed decreased lipogenesis and reduced expression levels of acetyl-CoA carboxylase, fatty acid synthase, and stearol-CoA desaturase. We further demonstrated that expression levels of sterol response element binding protein 1c was significantly decreased in Cideb-deficient mice.


CONCLUSIONS
Our data demonstrate that Cideb is a novel important regulator in lipid metabolism in the liver. Cideb may represent a new therapeutic target for the treatment of obesity, diabetes, and liver steatosis.
Li
John Zhong
JZ
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Ye
Jing
J
Xue
Bofu
B
Qi
Jingzhong
J
Zhang
Jing
J
Zhou
Zhihong
Z
Li
Qing
Q
Wen
Zilong
Z
Li
Peng
P
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C484761:Cideb protein, mouse; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase