Promotion of healthy adipose tissue remodeling ameliorates muscle inflammation in a mouse model of sarcopenic obesity

Yunlin Ge; Siqi Li; Tao Yao; Yuexiao Tang; Qiangyou Wan; Xiaoli Zhang; Jing Zhao; Mingliang Zhang; Mengle Shao; Lijun Wang; Ying Wu

doi:10.3389/fnut.2023.1065617

Promotion of healthy adipose tissue remodeling ameliorates muscle inflammation in a mouse model of sarcopenic obesity

Front Nutr. 2023 Feb 17:10:1065617. doi: 10.3389/fnut.2023.1065617. eCollection 2023.

Authors

Yunlin Ge¹, Siqi Li^{2

3}, Tao Yao⁴, Yuexiao Tang^{5

6}, Qiangyou Wan², Xiaoli Zhang², Jing Zhao⁷, Mingliang Zhang⁸, Mengle Shao², Lijun Wang^{9

10}, Ying Wu^{4

5

6}

Affiliations

¹ The Third Department of Orthopedics, The 903th Hospital of People's Liberation Army, Hangzhou, Zhejiang, China.
² CAS Key Laboratory of Molecular Virology and Immunology, The Center for Microbes, Development, and Health, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
⁵ Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
⁶ Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Hangzhou, Zhejiang, China.
⁷ Technology Service Center, Instrumental Analysis Platform, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
⁸ Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai, China.
⁹ Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
¹⁰ Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Abstract

A large subset of elders is classified as having sarcopenic obesity, a prevalence of obesity in combination with sarcopenia which places an aging population at the risk of adverse health consequences from both conditions. However, its complex etiology has restrained the development of effective therapeutic strategies. Recent progress has highlighted that the mode by which adipose tissue (AT) remodels is a determinant of metabolic health in the context of obesity. Healthy AT remodeling confers metabolic protection including insulin-sensitizing and anti-inflammatory effects to non-adipose tissues including skeletal muscle. Here, we employed a doxycycline-inducible adipocyte Hif1a knockout system to evaluate the muscle-protective effects associated with HIF1α inactivation-induced healthy AT remodeling in a model of sarcopenic obesity. We found that adipocyte HIF1α inactivation leads to improved AT metabolic health, reduced serum levels of lipids and pro-inflammatory cytokines, and increase of circulating adipokine (APN) in ovariectomized obese mice fed with obesogenic high-fat diet (HFD). Concomitantly, muscle inflammation is evidently lower in obese OVX mice when adipocyte HIF1α is inactivated. Furthermore, these protective effects against muscle inflammation can be mimicked by the administration of adiponectin receptor agonist AdipoRon. Collectively, our findings underscore the importance of AT metabolic health in the context of concurrent sarcopenia and obesity, and promotion of healthy AT remodeling may represent a new therapeutic strategy to improve muscle health in sarcopenic obesity.

Keywords: HIF1α; adiponectin; adipose tissue remodeling; muscle inflammation; sarcopenic obesity.

Grants and funding

This work was supported by the grants from Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents to YW, from the National Natural Science Foundation of China (82170891, 81972674, 31900543, and 32200932) to MS, YW, and QW, and from Shanghai Pujiang Program (21PJ1414600), Shanghai Municipal Science and Technology Major Project (2019SHZDZX02), and Shanghai Municipal Science and Technology Project (22140903200) to MS. QW was also supported by China Postdoctoral Science Foundation (2022M723265) and Shanghai Municipal Human Resources and Social Security Bureau (2022646).