Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen, Shengnan; Liao, Qiwen; Liu, Jingxin; Pan, Rui‐Le; Lee, Simon Ming‐Yuen; Lin, Ligen

doi:10.1002/jcsm.12393

Cited by 98 publications

(91 citation statements)

References 62 publications

(125 reference statements)

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“…In addition, dexamethasone-treated muscle cells are commonly used to study amyotrophy. Dexamethasone has been demonstrated to upregulate the ubiquitin-proteasome machinery through increased MAFbx and MuRF1 expression [119,128]. Exposure of C2C12 myotubes to dexamethasone robustly increased MAFbx, MuRF1, and myostatin expression [119,123], reduced diameter of myotubes and decreased MyoD and myogenin expression [123]; similar results were observed in L6 cells [122].…”

Section: Glucocorticoids (Gcs) and Dexamethasonementioning

confidence: 58%

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Mankhong

Kim

Moon

et al. 2020

Cells

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Sarcopenia has been defined as a progressive decline of skeletal muscle mass, strength, and functions in elderly people. It is accompanied by physical frailty, functional disability, falls, hospitalization, and mortality, and is becoming a major geriatric disorder owing to the increasing life expectancy and growing older population worldwide. Experimental models are critical to understand the pathophysiology of sarcopenia and develop therapeutic strategies. Although its etiologies remain to be further elucidated, several mechanisms of sarcopenia have been identified, including cellular senescence, proteostasis imbalance, oxidative stress, and “inflammaging.” In this article, we address three main aspects. First, we describe the fundamental aging mechanisms. Next, we discuss both in vitro and in vivo experimental models based on molecular mechanisms that have the potential to elucidate the biochemical processes integral to sarcopenia. The use of appropriate models to reflect sarcopenia and/or its underlying pathways will enable researchers to understand sarcopenia and develop novel therapeutic strategies for sarcopenia. Lastly, we discuss the possible molecular targets and the current status of drug candidates for sarcopenia treatment. In conclusion, the development of experimental models for sarcopenia is essential to discover molecular targets that are valuable as biochemical biomarkers and/or therapeutic targets for sarcopenia.

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Section: Glucocorticoids (Gcs) and Dexamethasonementioning

confidence: 58%

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Mankhong

Kim

Moon

et al. 2020

Cells

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“…The n value for each experiment was shown in the figure legend. This was based on our previous results (Shen, Liao, Liu, et al, ; Shen, Liao, Feng, et al, ) and also for the purpose of carrying out statistical analysis according to the guidelines of British Journal of Pharmacology (Curtis et al, ). Cells and mice were randomly assigned to each treatment group and experiment.…”

Section: Methodsmentioning

confidence: 99%

Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

Shen

Liao

Zhang

et al. 2019

British J Pharmacology

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Background and Purpose Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle–adipose tissue crosstalk. Experimental Approach The therapeutic effect of myricanol was evaluated on palmitic acid (PA)‐treated C2C12 myotubes and high‐fat diet (HFD)‐fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria‐related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit. Key Results Myricanol increased mitochondrial quantity and function through activating AMP‐activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin‐stimulated glucose uptake, in PA‐treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3‐L1 adipocytes. In HFD‐fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat. Conclusions and Implications Myricanol modulates skeletal muscle–adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity.

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“…A Seahorse Bioscience XF24-3 Extracellular Flux Analyzer (Agilent, Santa Clara, CA) was used to measure the oxygen consumption rate (OCR) as described previously [24]. AML12 were seeded in XF24-well microplates (Seahorse Bioscience, Billerica, MA) at 5 × 10 4 cells per well.…”

Section: Seahorse Analysismentioning

confidence: 99%

SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity

et al. 2019

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Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD + -dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. SIRT3 overexpression promoted macroautophagy in LDs from P/O-treated hepatocytes through activating AMP-activated protein kinase (AMPK) and unc-51-like kinase 1, to boost LDs digestion. Gain of SIRT3 expression stimulated the formation of lysosome-associated membrane protein 2A (LAMP-2A)-heat shock cognate 71 kDa protein (HSC70)-perilipin-2 (PLN2) complex, to promote CMA process and reduce the stability of LDs in hepatocytes. Moreover, SIRT3 reduced the expression of stearoyl-CoA desaturase 1, to suppress lipogenesis. In addition, SIRT3 overexpression promoted LDs dispersion on detyrosinated microtubules, and directly deacetylated long-chain acyl-CoA dehydrogenase to enhance mitochondrial energetics. Taken together, SIRT3 ameliorates lipotoxicity in hepatocytes, which might be a potential target for the treatment of nonalcoholic fatty liver disease.

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Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Cited by 98 publications

References 62 publications

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy

Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity

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