Ragland Kayla J, Travis Kipton B, Spry Emmalie R, Zaman Toheed, Lundin Pamela M, Vaughan Roger A
Department of Health and Human Performance, High Point University, High Point, NC 27268, USA.
Department of Chemistry, High Point University, High Point, NC 27268, USA.
Metabolites. 2025 May 13;15(5):322. doi: 10.3390/metabo15050322.
: Muscle loss during sarcopenia and atrophy is also commonly associated with age-related insulin resistance. Interestingly, branched-chain amino acids (BCAA) which are known for stimulating muscle protein synthesis are commonly elevated during insulin resistance and sarcopenic obesity. : This study investigated the effects of the interplay between atrophy and insulin resistance on insulin sensitivity, mitochondrial metabolism, and BCAA catabolic capacity in a myotube model of skeletal muscle insulin resistance. : C2C12 myotubes were treated with dexamethasone to induce atrophy. Insulin resistance was induced via hyperinsulinemia. Gene and expression were measured using qRT-PCR and Western blot, while mitochondrial and lipid content were assessed using fluorescent staining. Cell metabolism was analyzed via Seahorse metabolic assays. : Both dexamethasone-induced atrophy and insulin resistance independently reduced insulin-stimulated pAkt levels, as well as mitochondrial function and content. However, neither treatment affected gene or protein expression associated with mitochondrial biogenesis or content. Although dexamethasone independently reduced insulin sensitivity in otherwise previously insulin-sensitive cells, dexamethasone had no significant effect on extracellular BCAA content. : Our findings indicate the metabolic interplay between atrophy and insulin resistance and demonstrate that both can reduce mitochondrial function, though only limited effects were observed on indicators of BCAA catabolism and utilization. This emphasizes the need for future studies to investigate the mechanisms that underlie atrophy and other metabolic disorders to develop new interventions.
肌肉减少症和萎缩过程中的肌肉流失也通常与年龄相关的胰岛素抵抗有关。有趣的是，以刺激肌肉蛋白质合成而闻名的支链氨基酸（BCAA）在胰岛素抵抗和肌肉减少性肥胖期间通常会升高。本研究在骨骼肌胰岛素抵抗的肌管模型中，研究了萎缩与胰岛素抵抗之间的相互作用对胰岛素敏感性、线粒体代谢和BCAA分解代谢能力的影响。用 dexamethasone 处理 C2C12 肌管以诱导萎缩。通过高胰岛素血症诱导胰岛素抵抗。使用 qRT-PCR 和蛋白质免疫印迹法测量基因和表达，同时使用荧光染色评估线粒体和脂质含量。通过海马代谢分析来分析细胞代谢。dexamethasone 诱导的萎缩和胰岛素抵抗均独立降低了胰岛素刺激的 pAkt 水平，以及线粒体功能和含量。然而，两种处理均未影响与线粒体生物发生或含量相关的基因或蛋白质表达。尽管 dexamethasone 在原本胰岛素敏感的细胞中独立降低了胰岛素敏感性，但 dexamethasone 对细胞外 BCAA 含量没有显著影响。我们的研究结果表明了萎缩与胰岛素抵抗之间的代谢相互作用，并证明两者均可降低线粒体功能，尽管在 BCAA 分解代谢和利用指标上仅观察到有限的影响。这强调了未来研究需要探究萎缩及其他代谢紊乱背后的机制，以开发新的干预措施。
