Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control in STZ‐Induced Diabetic Mice

Abstract

ScopeIn this study, we aim to determine the effects of resveratrol (RSV) on muscle atrophy in streptozocin‐induced diabetic mice and to explore mitochondrial quality control (MQC) as a possible mechanism.Methods and resultsThe experimental mice were fed either a control diet or an identical diet containing 0.04% RSV for 8 weeks. Examinations were subsequently carried out, including the effects of RSV on muscle atrophy and muscle function, as well as on the signaling pathways related to protein degradation and MQC processes. The results show that RSV supplementation improves muscle atrophy and muscle function, attenuates the increase in ubiquitin and muscle RING‐finger protein‐1 (MuRF‐1), and simultaneously attenuates LC3‐II and cleaved caspase‐3 in the skeletal muscle of diabetic mice. Moreover, RSV treatment of diabetic mice results in an increase in mitochondrial biogenesis and inhibition of the activation of mitophagy in skeletal muscle. RSV also protects skeletal muscle against excess mitochondrial fusion and fission in the diabetic mice.ConclusionThe results suggest that RSV ameliorates diabetes‐induced skeletal muscle atrophy by modulating MQC.

Transcutaneous carbon dioxide attenuates impaired oxidative capacity in skeletal muscle in hyperglycemia model

“…Many studies have reported that PGC-1α is an important regulator of oxidative capacity in skeletal muscle (Zechner et al 2010;Tadaishi et al 2011;Kang et al 2012). In the present study, the activity of CS, an indicator of oxidative capacity, and expression of COX-4, an enzyme of the mitochondrial respiratory chain, in the skeletal muscle were decreased in rats with STZ-induced hyperglycemia (Figure 2), which is consistent with previous reports (Py et al 2002;Roberts-Wilson et al 2010;Padrão et al 2012;Wang et al 2018). Additionally, the expression level of PGC-1α in the STZ/CO 2 (-) group was significantly decreased compared with that in the CON/CO 2 (-) group (Figure 3).…”

“…It is critically regulated by mitochondrial function represented by adenosine triphosphate synthesis through the tricarboxylic acid cycle. Muscle oxidative capacity depends on mitochondrial enzymatic activity and biogenesis (Short et al 2003;White and Schenk 2012), both of which are decreased by hyperglycemia in diabetes (Patti et al 2003;Boushel et al 2007;Fujimaki and Kuwabara 2017;Wang et al 2018), leading to the decrement of exercise capacity. Therefore, attenuation of hyperglycemia-induced impairment of muscle oxidative capacity is important to maintain exercise capacity.…”

“…On the other hand, a decrease in PGC-1α expression has been shown to lower muscle oxidative capacity (Leone et al 2005;Vainshtein et al 2015). It has been reported that low muscle oxidative capacity in diabetes is associated with decreased PGC-1α expression (Nagatomo et al 2011;Wang et al 2018). Therefore, it would be beneficial to attenuate the decrease in PGC-1α expression in order to suppress the decline of muscle oxidative capacity due to hyperglycemia.…”

Effects of Plant and Animal Natural Products on Mitophagy

“…In patients with diabetes, skeletal muscle dysfunction due to mitochondrial deficits may occur, leading to reduced muscle strength. Particularly, mitochondrial homeostasis and mitochondrial quality control are essential for the maintenance of muscle mass since they indirectly control myocyte insulin sensitivity [70].…”

“…Accordingly, resveratrol reduced the expression of two muscle-specific E3 ubiquitin ligases, that is, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING-finger protein-1 (MuRF-1), and the expression of LC3-II and cleaved caspase-3. In addition, resveratrol increased the expression of nuclear respiratory factor-(NRF-) 1, cytochrome c oxidase (Cox) IV, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and mitochondrial transcription factor A (mtTFA) and reduced the expression of mitochondrial fission regulatory proteins (e.g., phosphodynamin-related protein 1 (p-DRP1), mitochondrial fission 1 protein (FIS1), and mitochondrial fission factor (MFF)) and mitochondrial fusion regulatory proteins (e.g., p-DRP1 (Ser637), mitofusin-2 (MFN2), and OPA1 mitochondrial dynamin like GTPase (OPA1)) [70].…”