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Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice
Xiong, Yan1,2; Wu, Zihuan1; Zhang, Bin1; Wang, Chao3; Mao, Fengyi1,3; Liu, Xiao4,5; Hu, Keping1; Sun, Xiaobo1; Jin, Wen1; Kuang, Shihuan3
2019-05-01
发表期刊FASEB JOURNAL
ISSN0892-6638
卷号33期号:5页码:5876-5886
通讯作者Jin, Wen(wjin@implad.ac.cn) ; Kuang, Shihuan(skuang@purdue.edu)
摘要Fibronectin type III domain containing 5 (Fndc5) is a transmembrane protein highly expressed in the skeletal muscle. It was reported that exercise promotes the shedding of the extracellular domain of Fndc5, generating a circulating peptide (irisin) that cross-talks to adipose tissues to convert lipid-storing white adipocytes to energy-catabolizing beige adipocytes. However, the requirement of Fndc5 in mediating the beneficial effect of exercise remains to be determined. Here, we created a mouse model of Fndc5 mutation through transcription activator-like effector nuclease-mediated DNA targeting. The Fndc5 mutant mice have normal skeletal muscle development, growth, regeneration, as well as glucose and lipid metabolism at resting state, even when fed a high-fat diet. In response to running exercise, however, the Fndc5 mutant mice exhibit reduced glucose tolerance and insulin sensitivity and have lower maximal oxygen consumption compared with the exercised wild-type mice. Mechanistically, Fndc5 mutation attenuates exercise-induced browning of white adipose tissue that is crucial for the metabolic benefits of physical activities. These data provide genetic evidence that Fndc5 is dispensable for muscle development and basal metabolism but essential for exercise-induced browning of white adipose tissues in mice.Xiong, Y., Wu, Z., Zhang, B., Wang, C., Mao, F., Liu, X., Hu, K., Sun, X., Jin, W., Kuang, S. Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice.
关键词irisin WAT metabolism Ucp1 beige adipocyte
DOI10.1096/fj.201801754RR
收录类别SCI
语种英语
资助项目National Natural Science Foundation of China[81471070] ; National Natural Science Foundation of China[41676152] ; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)[2016-I2M-1-012] ; Fundamental Research Funds for the Central Universities[2018NQN34] ; U.S. Department of Agriculture[NC1184] ; National Natural Science Foundation of China[81471070] ; National Natural Science Foundation of China[41676152] ; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)[2016-I2M-1-012] ; Fundamental Research Funds for the Central Universities[2018NQN34] ; U.S. Department of Agriculture[NC1184]
WOS研究方向Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Biology ; Cell Biology
WOS记录号WOS:000466932600007
出版者FEDERATION AMER SOC EXP BIOL
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被引频次:37[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.qdio.ac.cn/handle/337002/157055
专题实验海洋生物学重点实验室
通讯作者Jin, Wen; Kuang, Shihuan
作者单位1.Chinese Acad Med Sci, Inst Med Plant Dev, Beijing, Peoples R China
2.Southwest Minzu Univ, Coll Life Sci & Technol, Key Lab Qinghai Tibetan Plateau Anim Genet Resour, Minist Educ, Chengdu, Sichuan, Peoples R China
3.Purdue Univ, Dept Anim Sci, 270 S Russell St,2070 CRTN, W Lafayette, IN 47907 USA
4.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Shandong, Peoples R China
5.Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao, Shandong, Peoples R China
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Xiong, Yan,Wu, Zihuan,Zhang, Bin,et al. Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice[J]. FASEB JOURNAL,2019,33(5):5876-5886.
APA Xiong, Yan.,Wu, Zihuan.,Zhang, Bin.,Wang, Chao.,Mao, Fengyi.,...&Kuang, Shihuan.(2019).Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice.FASEB JOURNAL,33(5),5876-5886.
MLA Xiong, Yan,et al."Fndc5 loss-of-function attenuates exercise-induced browning of white adipose tissue in mice".FASEB JOURNAL 33.5(2019):5876-5886.
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