Sarcopenic obesity: emerging mechanisms and therapeutic potential

Abstract

Sarcopenic obesity, or the loss of muscle mass and function associated with excess adiposity, is a largely untreatable medical condition associated with diminished quality of life and increased risk of mortality. To date, it remains somewhat paradoxical and mechanistically undefined as to why a subset of adults with obesity develop muscular decline, an anabolic stimulus generally associated with retention of lean mass. Here, we review evidence surrounding the definition, etiology, and treatment of sarcopenic obesity with an emphasis on emerging regulatory nodes with therapeutic potential. We review the available clinical evidence largely focused on diet, lifestyle, and behavioral interventions to improve quality of life in patients with sarcopenic obesity. Based upon available evidence, relieving consequences of energy burden, such as oxidative stress, myosteatosis, and/or mitochondrial dysfunction, is a promising area for therapeutic development in the treatment and management of sarcopenic obesity.

Keywords: Aging; Mitochondrial quality control; Muscle function; Muscle mass; Obesity; Sarcopenia; Sarcopenic obesity.

Fig. 1.. Working model of sarcopenic obesity.

Obesity in the background of aging exacerbates energy imbalance, resulting in excessive mitochondrial fission, declining quality control, and increased oxidative stress. In turn, regenerative functions within skeletal muscle decline, including decreased proliferative potential, myotube maturation, and protein turnover. In result, skeletal muscle function declines, resulting in frailty, decreased force production, and diminished locomotor function.

Fig. 2.. Emerging cellular therapies for sarcopenic obesity.

Pharmacological strategies that enhance muscle function directly by enhancing cellular quality control or indirectly by alleviating energy burden work synergistically to abrogate the physiological consequences of sarcopenic obesity.