Short‐chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice

作者：Chaoran Liu, Pui Yan Wong, Qianjin Wang, Hei Yuet Wong, Tao Huang, Can Cui, Ning Zhang, Wing‐Hoi Cheung, Ronald Man Yeung Wong · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2024 · DOI：10.1002/jcsm.13573 · 被引用次数：78 · 研究领域：Nutrition and Health in Aging、Muscle Physiology and Disorders、Muscle metabolism and nutrition

BACKGROUND: Sarcopenia is a prevalent muscle disorder in old people leading to higher fracture rate, mortality, and other adverse clinical outcomes. Evidence indicates that short-chain fatty acids (SCFAs), which are beneficial gut microbial metabolites, were reduced in old people with sarcopenia. This study aimed to determine whether the use of SCFAs as a supplement can be a therapeutic strategy of sarcopenia in a pre-clinical model. METHODS: Seven-month-old pre-sarcopenic senescent accelerated mouse prone 8 (SAMP8) mice received daily SCFAs cocktail (acetate, butyrate, and propionate) for 3 months. Age-matched senescence accelerated mouse resistant 1 (SAMR1) and SAMP8 mice receiving sodium-matched drinking water were control groups. The gut microbiota composition analysis of aged mice with or without sarcopenia was conducted by 16S rDNA sequencing. Gut barrier-related proteins and lipopolysaccharide (LPS) concentration were biomarkers of gut permeability. Colon inflammation levels, circulatory SCFAs concentration, muscle quality, function, and underlying pathways were detected by cell number counting, RT-qPCR, gas chromatography-mass spectrometry, measurements of muscle wet weight and grip strength, ex vivo functional test, treadmill endurance test, transcriptomic sequencing, morphological and immunofluorescent staining, as well as western blot. To investigate the role of mTOR signalling pathways in SCFAs treatment, C2C12 myotubes were treated with rapamycin. RESULTS: Aged S...