Loss of Adipose Growth Hormone Receptor in Mice Enhances Local Fatty Acid Trapping and Impairs Brown Adipose Tissue Thermogenesis

Liyuan Ran, Xiaoshuang Wang, Ai Mi, Yanshuang Liu, Jin Wu, Haoan Wang, Meihua Guo, Jie Sun, Bo Liu, Youwei Li, Dan Wang, Rujiao Jiang, Ning Wang, Wenting Gao, Li Zeng, Lin Huang, Xiaoli Chen, Derek LeRoith, Bin Liang, Xin LiYingjie Wu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD.

Original languageEnglish (US)
Pages (from-to)106-121
Number of pages16
JournaliScience
Volume16
DOIs
StatePublished - Jun 28 2019

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (No. 81600668 ; No. 81471000l ); the Ministry of Science and Technology of China (No. 2014DFA32120 ); and Research Project of Educational Commission of Liaoning , China (No. L2016023 ).

Funding Information:
This work was supported by the National Natural Science Foundation of China (No. 81600668; No. 81471000l); the Ministry of Science and Technology of China (No. 2014DFA32120); and Research Project of Educational Commission of Liaoning, China (No.L2016023). Y.W. and L.R. conceived the study, designed the experiments, and wrote the manuscript. L.R. and X.W. performed experiments and collected and analyzed data. A.M. Y.L. and H.W. performed cold and cell experiments. J.W. J.S. and B.L. assisted with the qPCR and western Blot. M.G. D.W. W.G. and Y.L. performed animal breeding. R.J. and N.W. assisted with histological experiments. L.Z. L.H. X.C. B.L. and X.L. also designed the experiments and involved in discussion and writing the manuscript. L.Z. D.L. and X.L. provided language help. All authors reviewed the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • Cellular Physiology
  • Diabetology
  • Endocrinology
  • Physiology

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