Resveratrol prevents sarcopenic obesity by reversing mitochondrial dysfunction and oxidative stress via the PKA/LKB1/AMPK pathway

Abstract

Background: The concept of sarcopenic obesity refers to low muscle mass coupled with high adiposity in older adults. Sarcopenic obesity is a new medical challenge that imposes tremendous financial burdens on healthcare authorities worldwide. This study investigated the effects of resveratrol on high-fat diet-induced sarcopenic obesity in aged rats and palmitate acid-induced muscle atrophy in L6 myotubes and explored the underlying mechanisms. Results: In vivo , resveratrol prevented muscle loss and myofiber size decrease, improved grip strength and abolished excessive fat accumulation. In vitro , resveratrol inhibited the palmitate acid-mediated reductions in myosin heavy chain content and myotube diameter. Moreover, resveratrol ameliorated mitochondrial dysfunction and oxidative stress, leading to an improvement in protein metabolism and contributing to the prevention of muscle atrophy. Furthermore, the protective effects of resveratrol on mitochondrial function, oxidative stress and muscle atrophy were abolished by PKA siRNA, LKB1 siRNA and AMPK siRNA transfection in vitro . Conclusions: Resveratrol prevented high-fat diet-induced muscle atrophy in aged rats by reversing mitochondrial dysfunction and oxidative stress, which was partially mediated by the PKA/LKB1/AMPK pathway. These findings indicate that resveratrol might have potential uses for the prevention and treatment of sarcopenic obesity.

<p>The Mechanism of Traditional Chinese Medicine for the Treatment of Obesity</p>

“…Therefore, in the early stage of increased insulin secretion, properly reducing the level of insulin can improve insulin sensitivity and achieve the purpose of weight loss. 90 In addition, some studies have suggested that resveratrol 91 can improve mitochondrial dysfunction, increase muscle content, reduce fat and lose weight. But it is not clear whether these herbs first improve obesity and then improve the metabolism of these tissues, or whether they first improve the metabolism of these tissues and then improve obesity.…”

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

“…AMPK, a regulator of cellular energy homeostasis [213], is triggered by energy stress signalled by reduced ATP and increased AMP levels [211]. AMPK is also activated by phosphorylation of two regulatory subunits by several kinases, including the energy stress-sensitive LKB [214], PKA [215], and the CAMM-GSK3β axis [216] as well as by other factors, including PPARα, associated with lipid metabolism [217] and hypoxia [218]. AMPK triggers the expression of antioxidant enzymes, notably HO-1, through Nrf2 [219,220], and improves the control of proteostasis [221] through direct activation of FOXO3 [222] and ULK1 [223] and by indirect activation of TFEB [224]; AMPK activation also improves both glucose metabolism by favoring GLUT4 translocation to the membrane [225,226] and lipid metabolism through PPARα.…”

“…Molecular chaperones, in particular Some of the mechanisms reported above are also triggered by plant polyphenols. In particular, it has been reported that OLE increases intracellular free Ca 2+ levels from the internal stores with ensuing activation of the calcium-CAMMK-GSK3β pathway [216] and reduces oxidative stress through AMPK-dependent activation of HO-1 [219], whereas in aged rats, resveratrol protects against high-fat diet-induced muscle atrophy counteracting PKA/LKB1/AMPK-mediated mitochondrial dysfunction and oxidative stress [215]. Finally, plant polyphenols including quercetin, resveratrol, and catechins activate SIRT1, a class-3 histone deacetylase involved in several aging-related pathologies, including neurodegeneration [228].…”

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

“…Furthermore, resveratrol administrated to the pregnant and lactating mice led to promoted white adipose browning and thermogenesis in the male descendants, and these health benefits persisted and prevented obesity in their future life [99]. In addition, resveratrol protected against sarcopenic obesity by improving mitochondrial function and reducing oxidative stress through the PKA/liver kinase B1 (LKB1)/AMPK pathway [100]. Resveratrol also showed positive impacts on obesity-related complications, such as reproductive dysfunction like infertility and endocrine disorders [101,102].…”

“…In vitro: Improving mitochondrial function and reducing oxidative stress through the PKA/LKB1/AMPK pathway; In vivo: Preventing muscle loss and myofiber size decrease, improving grip strength, and abolishing excessive fat accumulation [100] In vivo Mice 0.06% diet Improving obesity-related complications by restoring plasma thyroid hormone levels, and attenuating oxidative stress in the heart [101] In…”