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Cidea-deficient mice have lean phenotype and are resistant to obesity

Abstract

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.

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Figure 1: Cidea is highly expressed in BAT.
Figure 2: Targeted disruption of Cidea.
Figure 3: Higher core body temperature, metabolic rate and lipolysis in BAT of Cidea-null (−/−) mice relative to wild-type (+/+) mice.
Figure 4: Less adiposity and lean phenotype in Cidea-null mice (−/−) compared with wild-type (+/+) mice.
Figure 5: Cidea interacts with Ucp1 and inhibits its uncoupling activity in yeast.

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Acknowledgements

We thank B. Tang and E. Manser for their critical comments on the manuscript; D. Lai for help in statistical analysis; S. Moochhala for providing the animal metabolic facility; H. Horstmann, L. Hwang, H. Lu, H. Ng, B. Chua, G. Zeng and E. Wong for technical help; and W. Hofmann for his suggestions. This work was supported by Agency for Science, Technology and Research in Singapore.

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Correspondence to Peng Li.

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Zhou, Z., Yon Toh, S., Chen, Z. et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat Genet 35, 49–56 (2003). https://doi.org/10.1038/ng1225

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