Dihydromyricetin prevents obesity-induced slow-twitch-fiber reduction partially via FLCN/FNIP1/AMPK pathway

Zhou, Quanhong; Gu, Yeyun; Wang, Xiaolan; Chen, Ka; Gong, Xinhua; Zhou, Min; Ran, Li; Zhu, Jingjing; Mi, Mantian

doi:10.1016/j.bbadis.2017.03.019

Cited by 33 publications

(36 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DM displays a broad range of biological and pharmacological activities such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective and hepatoprotective effects [17][18][19][20][21]. Our previous studies demonstrated that DM could improve skeletal muscle insulin resistance and stimulate myokine secretion [22][23][24]. Importantly, we verified that DM could reverse mitochondrial dysfunction in skeletal muscle under acute hypoxic conditions, which contributes to improvements in physical performance [25].…”

Section: Introductionsupporting

confidence: 63%

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Huang¹,

Chen²,

Ren³

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Skeletal muscle atrophy is an important health issue and can impose tremendous economic burdens on healthcare systems. Glucocorticoids (GCs) are well-known factors that result in muscle atrophy observed in numerous pathological conditions. Therefore, the development of effective and safe therapeutic strategies for GC-induced muscle atrophy has significant clinical implications. Some natural compounds have been shown to effectively prevent muscle atrophy under several wasting conditions. Dihydromyricetin (DM), the most abundant flavonoid in Ampelopsis grossedentata, has a broad range of health benefits, but its effects on muscle atrophy are unclear. The purpose of this study was to evaluate the effects and underlying mechanisms of DM on muscle atrophy induced by the synthetic GC dexamethasone (Dex). Methods: The effects of DM on Dex-induced muscle atrophy were assessed in Sprague-Dawley rats and L6 myotubes. Muscle mass and myofiber cross-sectional areas were analyzed in gastrocnemius muscles. Muscle function was evaluated by a grip strength test. Myosin heavy chain (MHC) content and myotube diameter were measured in myotubes. Mitochondrial morphology was observed by transmission electron microscopy and confocal laser scanning microscopy. Mitochondrial DNA (mtDNA) was quantified by real-time PCR. Mitochondrial respiratory chain complex activities were examined using the MitoProfile Rapid Microplate Assay Kit, and mitochondrial membrane potential was assessed by JC-1 staining. Protein levels of mitochondrial biogenesis and dynamics markers were detected by western blotting. Myotubes were transfected with siRNAs targeting peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM) and mitofusin-2 (mfn2) to determine the underlying mechanisms. Results: In vivo, DM preserved muscles from weight and average fiber cross-sectional area losses and improved grip strength. In vitro, DM prevented the decrease in MHC content and myotube diameter. Moreover, DM stimulated mitochondrial biogenesis and promoted mitochondrial fusion, rescued the reduced mtDNA content, improved mitochondrial morphology, prevented the collapse in mitochondrial membrane potential and enhanced mitochondrial respiratory chain complex activities; these changes restored mitochondrial function and improved protein metabolism, contributing to the prevention of Dex-induced muscle atrophy. Furthermore, the protective effects of DM on mitochondrial function and muscle atrophy were alleviated by PGC-1α siRNA, TFAM siRNA and mfn2 siRNA transfection in vitro. Conclusion: DM attenuated Dex-induced muscle atrophy by reversing mitochondrial dysfunction, which was partially mediated by the PGC-1α/TFAM and PGC-1α/mfn2 signaling pathways. Our findings may open new avenues for identifying natural compounds that improve mitochondrial function as promising candidates for the management of muscle atrophy.

show abstract

Section: Introductionsupporting

confidence: 63%

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Huang¹,

Chen²,

Ren³

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, we showed that leucine significantly increased the activities of MDH and SDH in porcine skeletal muscle satellite cells. Sirt1 and AMPK play a key role in fiber‐type specification (Chalkiadaki, Igarashi, Nasamu, Knezevic, & Guarente, ; Zhou et al., ). In this study, we showed that leucine significantly increased the protein levels of Sirt1 and phospho‐AMPK.…”

Section: Discussionmentioning

confidence: 99%

Leucine regulates slow‐twitch muscle fibers expression and mitochondrial function by Sirt1/AMPK signaling in porcine skeletal muscle satellite cells

Chen

Xiang

Jia

et al. 2018

Animal Science Journal

View full text Add to dashboard Cite

A previous study demonstrated that leucine upregulates the slow myosin heavy chain mRNA expression in C2C12 cells. However, the role of leucine in slow-twitch muscle fibers expression and mitochondrial function of porcine skeletal muscle satellite cells as well as its mechanism remain unclear. In this study, porcine skeletal muscle satellite cells cultured in differentiation medium were treated with 2 mM leucine for 3 days. Sirt1 inhibitor EX527, AMPK inhibitor compound C, and AMPKα1 siRNA were used to examine its underlying mechanism. Here we showed that leucine increased slow-twitch muscle fibers and mitochondrial function-related gene expression, as well as increased succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities. Moreover, leucine increased the protein levels of Sirt1 and phospho-AMPK. We also found that AMPKα1 siRNA, AMPK inhibitor compound C, or Sirt1 inhibitor EX527 attenuated the positive effect of leucine on slow-twitch muscle fibers and mitochondrial function-related gene expression. Finally, we showed that Sirt1 was required for leucine-induced AMPK activation. Our results provide, for the first time, evidence that leucine induces slow-twitch muscle fibers expression and improves mitochondrial function through Sirt1/AMPK signaling pathway in porcine skeletal muscle satellite cells. K E Y W O R D Sleucine, mitochondrial function, porcine skeletal muscle satellite cells, Sirt1/AMPK, slowtwitch muscle fibers expression

show abstract

“…The determination of mitochondrial DNA copy number was performed as described previously [52]. Briefly, mtDNA was extracted from soleus muscles and C2C12 myotubes using the Mito DNA Extraction Kit (Genmed Scientifics Inc., Wilmington, MD, USA) according to the manufacturer's instructions.…”

Section: Determination Of Mitochondrial Dna Copy Numbermentioning

confidence: 99%

Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

It has been demonstrated that skeletal muscle adaptions, including muscle fibers transition, angiogenesis, and mitochondrial biogenesis are involved in the regular exercise-induced improvement of endurance capacity and metabolic status. Herein, we investigated the effects of pterostilbene (PST) supplementation on skeletal muscle adaptations to exercise training in rats. Six-week-old male Sprague Dawley rats were randomly divided into a sedentary control group (Sed), an exercise training group (Ex), and exercise training combined with 50 mg/kg PST (Ex + PST) treatment group. After 4 weeks of intervention, an exhaustive running test was performed, and muscle fiber type transformation, angiogenesis, and mitochondrial content in the soleus muscle were measured. Additionally, the effects of PST on muscle fiber transformation, paracrine regulation of angiogenesis, and mitochondrial function were tested in vitro using C2C12 myotubes. In vivo study showed that exercise training resulted in significant increases in time-to-exhaustion, the proportion of slow-twitch fibers, muscular angiogenesis, and mitochondrial biogenesis in rats, and these effects induced by exercise training could be augmented by PST supplementation. Moreover, the in vitro study showed that PST treatment remarkably promoted slow-twitch fibers formation, angiogenic factor expression, and mitochondrial function in C2C12 myotubes. Collectively, our results suggest that PST promotes skeletal muscle adaptations to exercise training thereby enhancing the endurance capacity.

show abstract

Dihydromyricetin prevents obesity-induced slow-twitch-fiber reduction partially via FLCN/FNIP1/AMPK pathway

Cited by 33 publications

References 54 publications

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function via the PGC-1α Pathway

Leucine regulates slow‐twitch muscle fibers expression and mitochondrial function by Sirt1/AMPK signaling in porcine skeletal muscle satellite cells

Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats

Contact Info

Product

Resources

About