Azilsartan Ameliorates Skeletal Muscle Wasting in High Fat Diet (HFD)-induced Sarcopenic Obesity in Rats via Activating Akt Signalling Pathway

Abstract

An association between the loss of skeletal muscle mass and obesity in the geriatric population has been identified as a disease known as sarcopenic obesity. Therefore, therapeutic/preventive interventions are needed to ameliorate sarcopenia. The present study investigates the effect of azilsartan (AZL) on skeletal muscle loss in High-Fat Diet (HFD)-induced sarcopenic obese (SO) rats. Four- and fourteen-months male Sprague Dawley rats were used and randomized in control and azilsartan treatment. 14 months animals were fed with HFD for four months and labeled as HFD-fed SO rats. Young & old rats received 0.5% carboxymethyl cellulose as a vehicle/AZL (8 mg/kg, per oral) treatment for six weeks. Grip strength and body composition analysis were performed after the last dose of AZL. Serum and gastrocnemius (GN)muscles were collected after animal sacrifice. AZL treatment significantly increased lean muscle mass, grip strength, myofibrillar protein, and antioxidant (superoxide dismutase & nitric oxide) levels in SO rats. AZL also restored the muscle biomarkers (creatine kinase, myostatin & testosterone), and insulin levels. AZL improves cellular, and ultracellular muscle structure and prevents type I to type II myofiber transitions in SO rats. Further, immunohistochemistry results showed increased expressions of pAkt and reduced expression of MuRF-1 and TNF-α exhibiting that AZL intervention could decrease protein degradation in SO rats. In conclusion, present results showed that AZL significantly increased lean mass, and restored muscle biomarkers, and muscle architecture. Taken together, the aforementioned findings suggest that azilsartan could be a possible therapeutic approach to reduce muscle wasting in sarcopenic obesity.

Keywords: Akt; Azilsartan; High-Fat Diet (HFD); Muscle fiber; Sarcopenia obesity; Skeletal muscle.