Semaglutide-induced weight loss improves mitochondrial energy efficiency in skeletal muscle

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2025-04-20 DOI:10.1002/oby.24274

Ran Hee Choi, Takuya Karasawa, Cesar A. Meza, J. Alan Maschek, Allison M. Manuel, Linda S. Nikolova, Kelsey H. Fisher-Wellman, James E. Cox, Amandine Chaix, Katsuhiko Funai

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Abstract

Objective

Glucagon-like peptide-1 receptor agonists (e.g., semaglutide) potently induce weight loss, thereby reducing obesity-related complications. However, weight regain occurs when treatment is discontinued. An increase in skeletal muscle oxidative phosphorylation (OXPHOS) efficiency upon diet-mediated weight loss has been described, which may contribute to reduced systemic energy expenditure and weight regain. We set out to determine the unknown effect of semaglutide on muscle OXPHOS efficiency.

Methods

C57BL/6J mice were fed a high-fat diet for 12 weeks before receiving semaglutide or vehicle for 1 or 3 weeks. The rates of ATP production and oxygen (O₂) consumption were measured via high-resolution respirometry and fluorometry to determine OXPHOS efficiency in muscle at these two time points.

Results

Semaglutide treatment led to significant reductions in fat and lean mass. Semaglutide improved skeletal muscle OXPHOS efficiency, measured as ATP produced per O₂ consumed in permeabilized muscle fibers. Mitochondrial proteomic analysis revealed changes restricted to two proteins linked to complex III assembly (LYRM7 and TTC19; p < 0.05 without multiple corrections) without substantial changes in the abundance of OXPHOS subunits.

Conclusions

These data indicate that weight loss with semaglutide treatment increases skeletal muscle mitochondrial efficiency. Future studies could test whether it contributes to weight regain.

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semaglu肽诱导的体重减轻改善骨骼肌线粒体能量效率

目的胰高血糖素样肽-1受体激动剂（如semaglutide）能有效诱导体重减轻，从而减少肥胖相关并发症。然而，一旦停止治疗，体重就会反弹。在饮食介导的体重减轻中，骨骼肌氧化磷酸化（OXPHOS）效率增加，这可能有助于减少全身能量消耗和体重恢复。我们着手确定semaglutide对肌肉OXPHOS效率的未知影响。方法C57BL/6J小鼠先饲喂高脂饲料12周，再分别饲喂西马鲁肽或代药1、3周。通过高分辨率呼吸法和荧光法测量ATP产生率和氧（O2）消耗率，以确定这两个时间点肌肉中的OXPHOS效率。结果西马鲁肽治疗可显著降低脂肪和瘦肉质量。Semaglutide改善骨骼肌OXPHOS效率，以渗透肌纤维中消耗的每O2产生的ATP来衡量。线粒体蛋白质组学分析显示，变化仅限于与复合物III组装相关的两个蛋白(LYRM7和TTC19；p < 0.05，没有多次校正)，OXPHOS亚基的丰度没有实质性变化。结论：这些数据表明，用西马鲁肽治疗体重减轻可提高骨骼肌线粒体效率。未来的研究可以测试它是否会导致体重反弹。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.