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Browning of Pig White Preadipocytes by Co-Overexpressing Pig PGC-1 alpha and Mice UCP1

文献类型： 外文期刊

作者： Hou, Lianjie 1 ; Xie, Meiying 1 ; Cao, Lingbo 1 ; Shi, Jia 1 ; Xu, Guli 1 ; Hu, Chingyuan 2 ; Wang, Chong 1 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Natl Engn Res Ctr Breeding Swine Ind, Guangzhou, Guangdong, Peoples R China

2.Univ Hawaii Manoa, Coll Trop Agr &

关键词： Ucp1; Mitochondria; AMPK-SIRT1 pathway; PGC-1 alpha; Uncoupled respiration

期刊名称：CELLULAR PHYSIOLOGY AND BIOCHEMISTRY （ 2017影响因子：5.5； 五年影响因子：4.354 ）

ISSN： 1015-8987

年卷期： 2018 年 48 卷 2 期

页码：

收录情况： SCI

摘要： Background/Aims: Brown adipose tissue (BAT) is critical for mammals' survival in the cold environment. BAT-dependent non-shivering thermogenesis is attributed to uncoupling protein 1 (UCP1)'s disengagement of oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Thus individuals with a substantial amount of BAT are better equipped during cold stress and less likely to become obese. Recently, our laboratory has shown pig adipocytes have no UCP1 protein. The inability of newborn piglets to generate heat contributed to its high death rate. Repairing the genetic defect of UCP1 in pig adipocytes has implications in defending against cold for piglets and developing an alternative treatment for human obesity. Methods: Q-PCR, western blotting (WB) and oxygen consumption measurement were used to enable functional UCP1 protein in preadipocytes. Immunoprecipitation (IP), chromatin immunoprecipitation (CHIP), and dual-luciferase reporter assay system were used to clarify the thermogenesis mechanism of functional UCP1. Results: Only co-overexpressing mice UCP1 and pig PGC-1 alpha increased not only the mitochondrial number but also the uncoupled respiration rate in the transfected pig adipocytes. The functional mice UCP1 increased the pig PGC-1 alpha activity through the AMPK-SIRT1 pathway. The active form PGC-1 alpha interacted with transcription factors Lhx8, Zic1, ERR alpha, and PPAR alpha to regulate the expression of mitochondrial energy metabolism and adipocytes browning-related genes. Conclusion: Our data suggest a model in which pig PGC-1 alpha and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes. These results have great implications for piglet survival and developing an alternative treatment for human obesity in the future. (c) 2018 The Author(s) Published by S. Karger AG, Basel

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