Transcriptomic analysis of sarcopenic obese mice reveals alterations in regulators of muscle force production, such as extracellular matrix remodeling and shifts in muscle fiber type

Sarcopenic obesity (SO) is the combined condition of sarcopenia and obesity most commonly occurring in the older adult population. SO is associated with poor physical function, increased risk of musculoskeletal injury, and reduced quality of life and independence. There is little information on the molecular underpinnings of this condition. The aim of this study was to provide a transcriptomic analysis characterizing SO and to provide deeper understanding to the etiology of the condition. Young (Y) (6 mo) and aged (A) (21-24 mo) mice were fed either normal chow (L) (12% kcal from fat) or high-fat (O) (60% kcal from fat) diets ad libitum. Through multiple analyses, we observed genes related to ECM remodeling are downregulated with aged-obesity compared with young obesity, providing insight to the effects of age in a life-long obese condition. Furthermore, genes related to slow-twitch muscle contraction and fast-to-slow muscle fiber type transitions were upregulated in with obesity in the aged condition. Together, our results demonstrate avenues of dysregulation in SO skeletal muscle, providing the molecular building blocks expanding our understanding of the etiology of poor muscle function in this condition. Further understanding and exploration of these dysregulations is critical to identify therapeutic treatments targeting the source of muscle functional impairment, reducing the risk of musculoskeletal injury, and improving quality of life and independence SO individuals. Young (Y) (6 mo) and aged (A) (21-24 mo) mice were fed either normal chow (L) (12% kcal from fat) or high-fat (O) (60% kcal from fat) diets ad libitum. Tibialis anterior muscles were collected from young and age mice at expeerimental endpoint (young: 6 months old; aged 21-24 months old). Total RNA from the Tibialis anterior muscle underwent paired end mRNA sequencing.

肌肉减少症性肥胖（Sarcopenic obesity, SO）是肌肉减少症与肥胖合并存在的病症，最常发生于老年人群。该病症与躯体功能受损、肌肉骨骼损伤风险升高以及生活质量与独立能力下降密切相关。目前针对该病症的分子机制相关研究数据仍较为匮乏。本研究旨在开展转录组学分析（transcriptomic analysis）以表征肌肉减少症性肥胖，并深化对该病症病因学的理解。

研究选取6月龄青年（Y）小鼠与21-24月龄老年（A）小鼠，分别给予正常饲料（L，脂肪供能占比12%）或高脂饲料（O，脂肪供能占比60%）自由采食。通过多维度分析发现，与青年肥胖小鼠相比，老年肥胖小鼠的细胞外基质（Extracellular Matrix, ECM）重塑相关基因表达下调，这为理解终身肥胖状态下年龄带来的影响提供了新视角。此外，在老年肥胖小鼠中，慢肌收缩相关基因以及肌纤维快缩型向慢缩型转化的相关基因表达呈现上调趋势。

综上，本研究结果揭示了肌肉减少症性肥胖患者骨骼肌的多条失调通路，为深化对该病症肌肉功能受损的病因学理解提供了分子基础。进一步探究这些分子失调机制，对于识别靶向肌肉功能损伤根源的治疗手段、降低肌肉骨骼损伤风险以及改善肌肉减少症性肥胖个体的生活质量与独立能力均至关重要。

本研究再次选取6月龄青年与21-24月龄老年小鼠，分别饲喂正常饲料或高脂饲料自由采食。于实验终点采集青年（6月龄）与老年（21-24月龄）小鼠的胫前肌（Tibialis anterior）组织。提取胫前肌总RNA后进行双端（paired end）mRNA测序（mRNA sequencing）。