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. Overall design: 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.