Ge Yunlin, Li Siqi, Yao Tao, Tang Yuexiao, Wan Qiangyou, Zhang Xiaoli, Zhao Jing, Zhang Mingliang, Shao Mengle, Wang Lijun, Wu Ying
The Third Department of Orthopedics, The 903th Hospital of People's Liberation Army, Hangzhou, Zhejiang, China.
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.
Front Nutr. 2023 Feb 17;10:1065617. doi: 10.3389/fnut.2023.1065617. eCollection 2023.
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 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.
很大一部分老年人被归类为患有肌少症性肥胖，即肥胖与肌少症同时存在，这使老年人群面临两种疾病带来的不良健康后果风险。然而，其复杂的病因限制了有效治疗策略的发展。最近的进展突出表明，脂肪组织（AT）重塑的方式是肥胖背景下代谢健康的一个决定因素。健康的AT重塑赋予代谢保护作用，包括对包括骨骼肌在内的非脂肪组织的胰岛素增敏和抗炎作用。在此，我们采用强力霉素诱导的脂肪细胞敲除系统，在肌少症性肥胖模型中评估与缺氧诱导因子1α（HIF1α）失活诱导的健康AT重塑相关的肌肉保护作用。我们发现，在喂食致肥胖高脂饮食（HFD）的去卵巢肥胖小鼠中，脂肪细胞HIF1α失活导致AT代谢健康改善、血脂和促炎细胞因子血清水平降低以及循环脂联素（APN）增加。同时，当脂肪细胞HIF1α失活时，肥胖去卵巢小鼠的肌肉炎症明显减轻。此外，给予脂联素受体激动剂AdipoRon可模拟这些对肌肉炎症的保护作用。总的来说，我们的研究结果强调了在同时存在肌少症和肥胖的情况下AT代谢健康的重要性，促进健康的AT重塑可能代表了一种改善肌少症性肥胖患者肌肉健康的新治疗策略。
