Exercise attenuated muscle mass loss and lipid deposition in high-fat diet-induced sarcopenic obesity by activating the AMPK/ACC pathway and inhibiting ferroptosis.
Exercise mitigates high-fat diet-induced sarcopenic obesity in mice by activating the AMPK/ACC pathway and inhibiting ferroptosis.
Sarcopenic obesity, characterized by skeletal muscle loss concurrent with adipose tissue accumulation, has emerged as a global health threat. Exercise is established as an effective intervention; however, the molecular mechanisms underlying its protective effects remain incompletely defined. This study investigated whether exercise mitigates high-fat diet (HFD)-induced sarcopenic obesity, and whether the mechanism was related to the activation of the adenosine monophosphate-activated protein kinase (AMPK)/Acetyl-CoA carboxylase pathway (ACC) pathway and the inhibition of ferroptosis. Cell experiments demonstrated that palmitic acid induced ferroptosis in C2C12 mouse myoblasts. Animal experiments confirmed that HFD promoted skeletal muscle ferroptosis in C57BL/6 mice, evidenced by iron metabolism imbalance (solute carrier family 39 member14 upregulation, ferroportin downregulation), impaired antioxidant capacity (reduced glutathione, superoxide dismutase, glutathione peroxidase 4), and elevated lipid peroxidation (increased malondialdehyde). Meanwhile, both flat treadmill running and uphill treadmill running may reverse these changes by activating AMPK/ACC phosphorylation, reducing non-transferrin iron uptake, enhancing iron export and storage, and improving antioxidant status, jointly inhibiting ferroptosis and attenuating muscle mass loss and lipid deposition. These findings confirm that ferroptosis acts as one of the key pathogenic drivers in sarcopenic obesity and suggests that exercise may improve sarcopenic obesity by activating the AMPK/ACC pathway and inhibiting ferroptosis. This study provides novel mechanistic insights into exercise-mediated regulation of iron-lipid metabolism crosstalk and informs targeted interventions for sarcopenic obesity.
Ru et al. (Sat,) conducted a other in Sarcopenic obesity. Exercise (flat and uphill treadmill running) vs. High-fat diet without exercise was evaluated on Skeletal muscle ferroptosis, iron metabolism, antioxidant capacity, and lipid peroxidation. Exercise attenuated muscle mass loss and lipid deposition in high-fat diet-induced sarcopenic obesity by activating the AMPK/ACC pathway and inhibiting ferroptosis.