iScience (Jun 2019)
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 Li,
- Yingjie Wu
Affiliations
- Liyuan Ran
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Xiaoshuang Wang
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Ai Mi
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Yanshuang Liu
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China
- Jin Wu
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Haoan Wang
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Meihua Guo
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Jie Sun
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Bo Liu
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Youwei Li
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Dan Wang
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Rujiao Jiang
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Ning Wang
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Wenting Gao
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China
- Li Zeng
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China
- Lin Huang
- Department of Pathophysiology, Dalian Medical University, Dalian 116044, China
- Xiaoli Chen
- Department of Food Science and Nutrition, University of Minnesota, Twin Cities, MN, USA
- Derek LeRoith
- Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn Mount Sinai School of Medicine, New York 10029, USA
- Bin Liang
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China; Corresponding author
- Xin Li
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York 10010, USA; Department of Urology, New York University Langone Medical Center, New York 10016, USA; Perlmutter Cancer Institute, New York University Langone Medical Center, New York 10016, USA; Corresponding author
- Yingjie Wu
- Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China; National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian 116044, China; Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian 116044, China; College of Integrative Medicine, Dalian Medical University, Dalian 116044, China; Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn Mount Sinai School of Medicine, New York 10029, USA; Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York 10010, USA; Corresponding author
- Journal volume & issue
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Vol. 16
pp. 106 – 121
Abstract
Summary: 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. : Physiology; Cellular Physiology; Endocrinology; Diabetology Subject Areas: Physiology, Cellular Physiology, Endocrinology, Diabetology
