RNA analysis of diet-induced sarcopenic obesity in rats

• Published in: Archives of gerontology and geriatrics 2023-05, Vol.108, p.104920-104920, Article 104920
• Main Authors: Sun, Qian-qian, Zhu, Huan, Tang, Hui-yu, Liu, Yan-yan, Chen, Yan-yu, Wang, Shumeng, Qin, Yi, Gan, Hua-tian, Wang, Shuang
• Format: Article
• Language: English
• Subjects: Animals; Diet, High-Fat; High-fat diet; Humans; Male; MEF2C (myocyte enhancer factor 2C); Muscle, Skeletal - metabolism; Obesity - metabolism; Rats; Rats, Sprague-Dawley; RNA - metabolism; RNA analysis; Sarcopenia - complications; Sarcopenic obesity
• ISSN: 0167-4943; 1872-6976
• DOI: 10.1016/j.archger.2022.104920

•Sarcopenic Obesity (SO) model was established and validated successfully through high-fat diet in older rats.•RNA-seq analysis of muscle show that differential expressed genes (DEG) and alternative splicing events (ASE) mainly focus on inflammatory, immune-response and antigen processing and presentation.•MEF2C, as a core transcription factors that regulates skeletal muscle differentiation and growth, is found with significant alternative 3′ splice sites (A3SS) and down-regulated expression in SO. Obesity has been suggested as a risk factor for sarcopenia. Sarcopenic obesity (SO), as a new category of obesity, is a high-risk geriatric syndrome in elderly individuals. However, knowledge about the molecular pathomechanisms of SO is still sparse. In the present study, starting at 13 months, male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) and normal diet (ND) for 28 weeks to establish a rodent animal model of SO with an identical protocol, which was further assessed and verified as a successful SO model. Through RNA-seq analysis of gastrocnemius muscle in SO rats, we found that differentially expressed genes (DEGs) and alternative splicing events (ASEs) focused mainly on inflammatory, immune-response, skeletal muscle cell differentiation, fat cell differentiation and antigen processing and presentation. Furthermore, as the core regulation factor of skeletal muscle, the mef2c (myocyte enhancer Factor 2C) gene also has a significant alternative 3′ splice site (A3SS) and down-regulated expression in HFD-induced SO. The alternative genes targeted by mef2c identified by GO analysis were enriched in transcript regulation of RNA polymerase II promoter. In conclusion, these explorative findings in aging high-fat-fed rats might serve as a firm starting point for understanding the pathway and mechanism of sarcopenic obesity.