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Loss of Adipose GHR in Mice Enhances Local Fatty Acid Trapping and Impairs BAT Thermogenesis

44 Pages Posted: 9 Feb 2019 Sneak Peek Status: Published

See all articles by Liyuan Ran

Liyuan Ran

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Xiaoshuang Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Ai Mi

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Yanshuang Liu

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Jin Wu

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Meihua Guo

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Jie Sun

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Bo Liu

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Youwei Li

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases ; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dan Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Rujiao Jiang

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Ning Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Wenting Gao

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Li Zeng

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Lin Huang

Dalian Medical University, Department of Pathophysiology

Xiaoli Chen

University of Minnesota - Twin Cities - Department of Food Science and Nutrition

Derek LeRoith

Icahn Mount Sinai School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease

Bin Liang

Chinese Academy of Sciences (CAS) - Key Laboratory of Animal Models and Human Disease Mechanisms; Chinese Academy of Sciences (CAS) - Kunming Institute of Zoology

Xin Li

New York University (NYU), College of Dentistry, Department of Basic Science and Craniofacial Biology; New York University (NYU), Langone Medical Center, Department of Urology; New York University (NYU), Langone Medical Center, Laura and Isaac Perlmutter Cancer Center

Yingjie Wu

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases ; Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research; Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models; Dalian Medical University - College of Integrative Medicine; Icahn Mount Sinai School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease; New York University (NYU), College of Dentistry, Department of Basic Science and Craniofacial Biology

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Abstract

Growth hormone (GH) binds to its receptor GHR to exert its pleiotropic effects on growth and metabolism. Disproportionate 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 the dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing BAT burning and WAT browning induced by cold were retarded in absence of adipose GHR but was 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 signalling emulates a healthy obesity situation which has metabolic advantages against HFD.

Keywords: GHR, Adipose tissues specific knockout, Lipid metabolism, Thermogenesis, Stromal vascular fractions

Suggested Citation

Ran, Liyuan and Wang, Xiaoshuang and Mi, Ai and Liu, Yanshuang and Wu, Jin and Guo, Meihua and Sun, Jie and Liu, Bo and Li, Youwei and Wang, Dan and Jiang, Rujiao and Wang, Ning and Gao, Wenting and Zeng, Li and Huang, Lin and Chen, Xiaoli and LeRoith, Derek and Liang, Bin and Li, Xin and Wu, Yingjie, Loss of Adipose GHR in Mice Enhances Local Fatty Acid Trapping and Impairs BAT Thermogenesis (February 8, 2019). Available at SSRN: https://ssrn.com/abstract=3331242 or http://dx.doi.org/10.2139/ssrn.3331242
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Liyuan Ran

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Xiaoshuang Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Ai Mi

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Yanshuang Liu

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Jin Wu

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Meihua Guo

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Jie Sun

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Bo Liu

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Youwei Li

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Dan Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Rujiao Jiang

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Ning Wang

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Wenting Gao

Dalian Medical University - Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University - National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Dalian Medical University - Liaoning Provence Key Lab of Genome Engineered Animal Models

Dalian
China

Li Zeng

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research

Dalian
China

Lin Huang

Dalian Medical University, Department of Pathophysiology

Dalian
China

Xiaoli Chen

University of Minnesota - Twin Cities - Department of Food Science and Nutrition

MN
United States

Derek LeRoith

Icahn Mount Sinai School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease

New York, NY
United States

Bin Liang

Chinese Academy of Sciences (CAS) - Key Laboratory of Animal Models and Human Disease Mechanisms ( email )

No.32 Jiaochang Donglu
Kunming, Yunnan 650223
China

Chinese Academy of Sciences (CAS) - Kunming Institute of Zoology ( email )

52 Sanlihe Rd.
Datun Road, Anwai
Beijing, Xicheng District 100864
China

Xin Li

New York University (NYU), College of Dentistry, Department of Basic Science and Craniofacial Biology ( email )

New York, NY
United States

New York University (NYU), Langone Medical Center, Department of Urology ( email )

New York, NY
United States

New York University (NYU), Langone Medical Center, Laura and Isaac Perlmutter Cancer Center ( email )

20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Yingjie Wu (Contact Author)

Dalian Medical University, Institute for Genome Engineered Animal Models of Human Diseases ( email )

Dalian
China

Dalian Medical University, National Center of Genetically Engineered Animal Models for International Research ( email )

Dalian
China

Dalian Medical University, Liaoning Provence Key Lab of Genome Engineered Animal Models ( email )

Dalian
China

Dalian Medical University - College of Integrative Medicine ( email )

Dalian
China

Icahn Mount Sinai School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease ( email )

New York, NY
United States

New York University (NYU), College of Dentistry, Department of Basic Science and Craniofacial Biology ( email )

New York, NY
United States

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