28 | Impairment of skeletal muscle force and mitochondrial respiratory capacity precedes muscle mass loss in an aged murine model of diet-induced obesity

Clara Sciorati¹, R. De Lorenzo^1|2, A. Avola¹, M. Giovarelli³, C. De Palma³, E. Clementi³, C. Lanzani¹, P. Rovere-Querini^1|2 | ¹IRCCS San Raffaele Hospital Scientific Institute, Milan, Italy; ²Vita-Salute San Raffaele University, Milan, Italy; ³Department of Biomedical and Clinical Science, University of Milan, Italy.

Sarcopenic obesity (SO) is characterized by the coexistence of obesity and sarcopenia, conditions that synergistically exacerbate frailty, particularly in the elderly population. However, the mechanisms underlying the development of sarcopenia within the context of obesity remain poorly understood. It is well established that mitochondrial respiratory capacity in skeletal muscle declines with age, and it is plausible that this decline contributes to the pathogenesis of SO. In this study, using a diet-induced murine model of obesity, we investigated the progression of sarcopenia in obesity during aging, with a particular focus on skeletal muscle mitochondria. We analyzed 12-month-old female C57BL/6 mice fed either a high-fat diet (HFD; 60% of calories from fat) or a standard diet (SD; 10% of calories from fat) over a seven-month period. We monitored body weight and composition in vivo, muscle volume, muscle strength and endurance. At 1, 3, and 7 months of diet, muscles were collected from both HFD- and SD-fed mice for histological and molecular ex vivo analyses. We evaluated respiration, number, area, diameter of mitochindria and mitochondrial network. From the first month of HFD feeding, mice exhibited increased body weight and fat accumulation. Grip strength, used as an indicator of muscle function, was significantly reduced in HFD-fed mice after one month, with further decline observed at three months. By seven months, histological analysis revealed a marked reduction in myofiber cross-sectional area compared to SD-fed controls. Notably, mitochondrial respiratory capacity and mitochondrial number were initially elevated after one month of HFD but showed a significant decline by three months. These results suggest that early metabolic alterations in mitochondrial function contribute to the onset and progression of sarcopenia in the context of obesity.