Promotion of healthy adipose tissue remodeling ameliorates muscle inflammation in a mouse model of sarcopenic obesity.
Promotion of healthy adipose tissue remodeling ameliorates muscle inflammation in a mouse model of sarcopenic obesity.
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促进健康脂肪组织重塑改善肌肉减少性肥胖小鼠模型的肌肉炎症。
DOI：
10.3389/fnut.2023.1065617
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发表时间：
2023
影响因子：
5
通讯作者：
Wu, Ying
中科院分区：
文献类型：
--
作者：
Ge, Yunlin;Li, Siqi;Yao, Tao;Tang, Yuexiao;Wan, Qiangyou;Zhang, Xiaoli;Zhao, Jing;Zhang, Mingliang;Shao, Mengle;Wang, Lijun;Wu, Ying
老年人的一个大的子集被归类为患有肌肉减少性肥胖症，肥胖症与肌肉减少症的结合的流行，这使得老龄化人口处于来自这两种病症的不良健康后果的风险中。然而，其复杂的病因限制了有效治疗策略的发展。最近的进展已经强调，脂肪组织（AT）重塑的模式是肥胖背景下代谢健康的决定因素。健康的AT重塑赋予代谢保护，包括对非脂肪组织（包括骨骼肌）的胰岛素增敏和抗炎作用。在这里，我们采用了一种强力霉素诱导的脂肪细胞HIF 1a敲除系统，以评估肌肉减少性肥胖模型中与HIF 1 α失活诱导的健康AT重构相关的肌肉保护作用。我们发现，脂肪细胞HIF 1 α失活导致改善AT代谢健康，降低血脂和促炎细胞因子的血清水平，并增加循环脂肪因子（APN）在卵巢切除肥胖小鼠喂食致肥胖高脂饮食（HFD）。同时，当脂肪细胞HIF 1 α失活时，肥胖OVX小鼠的肌肉炎症明显降低。此外，这些对肌肉炎症的保护作用可以通过施用脂联素受体激动剂AdipoRon来模拟。总的来说，我们的研究结果强调了AT代谢健康在并发肌减少症和肥胖症的背景下的重要性，促进健康的AT重塑可能代表了一种新的治疗策略，以改善肌减少性肥胖症的肌肉健康。
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.
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影响因子：
64.5
作者：
Lee YS;Kim JW;Osborne O;Oh DY;Sasik R;Schenk S;Chen A;Chung H;Murphy A;Watkins SM;Quehenberger O;Johnson RS;Olefsky JM
通讯作者：
Olefsky JM
影响因子：
0.4
作者：
Doumatey, Ayo P.;Bentley, Amy R.;Rotimi, Charles N.
通讯作者：
Rotimi, Charles N.
影响因子：
8.8
作者：
Ahmad, Naseer;Kushwaha, Priyanka;Trivedi, Ritu
通讯作者：
Trivedi, Ritu
影响因子：
5.2
作者：
Geraci A;Calvani R;Ferri E;Marzetti E;Arosio B;Cesari M
通讯作者：
Cesari M
影响因子：
4.1
作者：
Bondanelli, M;Ambrosio, MR;degli Uberti, E
通讯作者：
degli Uberti, E