Cidea-deficient mice have lean phenotype and are resistant to obesity.
The thermogenic activity of brown adipose tissue (BAT), important for adaptive thermogenesis and energy expenditure, is mediated by the mitochondrial uncoupling protein1 (Ucp1) that uncouples ATP generation and dissipates the energy as heat. We show here that Cidea, a protein of unknown function sharing sequence similarity with the N-terminal region of DNA fragmentation factors Dffb and Dffa, is expressed at high levels in BAT. Cidea-null mice had higher metabolic rate, lipolysis in BAT and core body temperature when subjected to cold treatment. Notably, Cidea-null mice are lean and resistant to diet-induced obesity and diabetes. Furthermore, we provide evidence that the role of Cidea in regulating thermogenesis, lipolysis and obesity may be mediated in part through its direct suppression of Ucp1 activity. Our data thus indicate a role for Cidea in regulating energy balance and adiposity.
Zhou
Zhihong
Z
Laboratories of Apoptosis Regulation, Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117609, Singapore.
Yon Toh
Shen
S
Chen
Zhengming
Z
Guo
Ke
K
Ng
Chee Peng
CP
Ponniah
Sathivel
S
Lin
Sheng-Cai
SC
Hong
Wanjin
W
Li
Peng
P
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003001:Cloning, Molecular; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007473:Ion Channels; D008066:Lipolysis; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009765:Obesity; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013851:Thinness / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1
D051017:Apoptosis Regulatory Proteins; D001786:Blood Glucose; D002352:Carrier Proteins; C112510:Cidea protein, mouse; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D014280:Triglycerides; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1