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Cold adaptation in pigs depends on UCP3 in beige adipocytes Free
Jun Lin1,2,†, Chunwei Cao3,†, Cong Tao4,†, Rongcai Ye1,2, Meng Dong1,2, Qiantao Zheng2,3, Chao Wang4, Xiaoxiao Jiang1,2, Guosong Qin3, Changguo Yan5, Kui Li4, John R. Speakman6, Yanfang Wang4,*, Wanzhu Jin1,7,*, and Jianguo Zhao3,7,*
1 Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2 College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China
3 State Key Laboratory of Stem Cell and Reproductive Biology, Chinese Academy of Sciences, Beijing 100101, China
4 State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
5 Department of Animal Science, Yanbian University, Yanji 133002, China
6 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China 7 Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China † These authors contributed equally to this work. *Correspondence to:Yanfang Wang, E-mail: Wangyanfang@caas.cn; Wanzhu Jin, E-mail: Jinw@ioz.ac.cn; Jianguo Zhao, E-mail: zhaojg@ioz.ac.cn
J Mol Cell Biol, Volume 9, Issue 5, October 2017, 364-375,  https://doi.org/10.1093/jmcb/mjx018
Keyword: cold resistant, brown adipose tissue, beige adipocyte, Tibetan pig, thermogenesis

Pigs lack functional uncoupling protein 1 (UCP1) making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism(s) enabling such adaptation are currently unknown. Here, we show that this resistance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue (WAT) browning. In two cold-resistant breeds (Tibetan and Min), but not a cold-sensitive breed (Bama), WAT browning was induced after cold exposure. Beige adipocytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was significantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold-resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.