Reduced metabolic capacity in fast and slow skeletal muscle via oxidative stress and the energy‐sensing of AMPK/SIRT1 in malnutrition

Abstract

The effects of malnutrition on skeletal muscle result in not only the loss of muscle mass but also fatigue intolerance. It remains unknown whether the metabolic capacity is related to the fiber type composition of skeletal muscle under malnourished condition although malnutrition resulted in preferential atrophy in fast muscle. The purpose of the present study was to investigate the effects of metabolic capacity in fast and slow muscles via the energy‐sensing of AMPK and SIRT1 in malnutrition. Wistar rats were randomly divided into control and malnutrition groups. The rats in the malnutrition group were provided with a low‐protein diet, and daily food intake was limited to 50% for 12 weeks. Malnutrition with hypoalbuminemia decreased the body weight and induced the loss of plantaris muscle mass, but there was little change in the soleus muscle. An increase in the superoxide level in the plasma and a decrease in SOD‐2 protein expression in both muscles were observed in the malnutrition group. In addition, the expression level of AMPK in the malnutrition group increased in both muscles. Conversely, the expression level of SIRT1 decreased in both muscles of the malnutrition group. In addition, malnutrition resulted in a decrease in the expression levels of PGC‐1α and PINK protein, and induced a decrease in the levels of two key mitochondrial enzymes (succinate dehydrogenase and citrate synthase) and COX IV protein expression in both muscles. These results indicate that malnutrition impaired the metabolic capacity in both fast and slow muscles via AMPK‐independent SIRT1 inhibition induced by increased oxidative stress.

Characterization of the Skeletal Muscle Proteome in Undernourished Old Rats

“…Our analysis showed a lower abundance of most of the mitochondrial proteins in response to UND, as highlighted by the reduced levels of several key enzymes in the Krebs cycle, β-oxidation, and OXPHOS complexes in both PL and SOL muscles. In line with this analysis, previous reports have shown altered mitochondrial function in the skeletal muscle of malnourished rats [17,18,52,55]. Our results indicate that alteration in mitochondrial function during UND is further complicated by the decrease in mitochondrial content.…”

“…We found that UND had effects on the glycolytic PL muscle but had no significant effect on the oxidative SOL muscle. These findings are corroborated by previous data, demonstrating that UND does not affect muscle mass and protein synthesis in aged SOL muscle [17,25] and does not affect muscle mass and fiber CSA in adult SOL muscle [52]. Whether undernutrition affects the muscle fiber type composition remains undescribed.…”

Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction

“…Albumin plays an antioxidant role in blood vessels ( Taverna et al, 2013 ). ( Hirabayashi et al, 2021 ) reported that chronic malnutrition with hypoalbuminemia results in increased oxidative damage in skeletal muscle, and our results also confirm this. The present research explores, for the first time, the antioxidant effect of PF on skeletal muscle and TNF-α-treated C2C12 cells.…”

“…PGC-1α modulates mitochondrial dynamics and bioenergetics and increases mitochondrial mass and function, thereby enhancing the energy supply. The threonine 172 site and its phosphorylation play an essential role in the regulation of AMPK activity ( Hirabayashi et al, 2021 ). The AMPK signaling pathway mediates several beneficial functions, including ATP production, and maintains redox potential, which ensures optimal mitochondrial functioning.…”

“…SIRT1 has been reported to belong to the sirtuin family, resist metabolic disorders, cancer, and cardiac stress ( Cantó and Auwerx, 2012 ) and block the muscle-specific UPS proteins MAFbx and MuRF-1 ( Lee and Goldberg, 2013 ). Activation of SIRT1 might be beneficial for sarcopenic obesity ( Guo et al, 2021 ; You et al, 2021 ), malnutrition ( Hirabayashi et al, 2021 ) and glucocorticoid-induced atrophy. Our analysis revealed that the AMPK signaling pathway was activated by PF treatment, further revealing that SIRT1 and PGC-1α, located downstream of AMPK signaling pathway, were also upregulated in CKD muscles.…”