Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol

Kimball, Scot R.; Lang, Charles H.

doi:10.1146/annurev-nutr-071816-064642

Cited by 39 publications

(56 citation statements)

References 126 publications

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“…We found that compared to naïve animals, the ethanol‐exposed animals had difficulties in reaching the surface (Figure 1B). In humans, alcoholic skeletal myopathy leads to muscle fiber atrophy along with muscle weakness 3 . We thus compared the sizes of the striated body wall muscle cells in naïve and ethanol‐exposed animals.…”

Section: Resultsmentioning

confidence: 99%

“…The detrimental effects of acute and chronic alcohol consumption on liver, pancreas, and brain are well documented 1 . Chronic alcohol consumption also causes the loss of skeletal muscle strength and cardiac contractile function 2,3 . Alcoholic myopathy and cardiomyopathy, collectively called alcoholic striated muscle disease, are more prevalent than all inherited muscle disorders combined and have an incidence of 45%‐75% among chronic alcohol users 4 .…”

Section: Introductionmentioning

confidence: 99%

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Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Sheoran

Richmond

et al. 2020

FASEB j.

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Chronic excessive ethanol consumption has distinct toxic and adverse effects on a variety of tissues. In skeletal muscle, ethanol causes alcoholic myopathy, which is characterized by myofiber atrophy and the loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes toxicity in muscle is poorly understood. Here, we show that the nematode Caenorhabditis elegans exhibits the key features of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and induces the expression of protective genes, including oxidative stress response genes. In addition, ethanol exposure causes the fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol‐induced mitochondrial fragmentation is dependent on the mitochondrial fission factor DRP‐1 (dynamin‐related protein 1) and its receptor proteins on the outer mitochondrial membrane. Our data indicate that this fragmentation contributes to the activation of the mitochondrial unfolded protein response (UPR). We also found that robust, perpetual mitochondrial UPR activation effectively reduces muscle weakness caused by ethanol exposure. Our results strongly suggest that the modulation of mitochondrial stress responses may provide a method to ameliorate alcohol toxicity and damage to muscle.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Sheoran

Richmond

et al. 2020

FASEB j.

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“…Chronic alcohol abuse leads to skeletal and cardio myopathy in humans. It is also well known that striated muscles of alcoholic patients show abnormalities in mitochondrial structures, defects in myofibril contractility, and metabolic reprogramming (3). In this study we employed two methods to measure muscle function, thrashing and burrowing assays.…”

Section: Discussionmentioning

confidence: 99%

“…1B). In humans alcoholic skeletal myopathy leads to muscle fiber atrophy along with muscle weakness (3). We thus compared the sizes of striated body wall muscle cells in naïve and ethanol-exposed animals.…”

Section: Ethanol Causes Muscle Dysfunction In C Elegansmentioning

confidence: 99%

“…The detrimental effects of acute and chronic alcohol consumption on liver, pancreas, and brain are well documented (1). Chronic alcohol consumption also causes loss of skeletal muscle strength and cardiac contractile function (2,3). Alcoholic myopathy and cardiomyopathy, collectively called alcoholic striated muscle disease, are more prevalent than all other inherited muscle disorders combined, with the incidence of 45-75% of chronic alcohol users (4).…”

Section: Introductionmentioning

confidence: 99%

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Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Hong-kyun

2019

Preprint

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AbstractsChronic excessive ethanol consumption produces distinct toxic and adverse effects on different tissues. In skeletal muscle ethanol causes alcoholic myopathy characterized by myofiber atrophy and loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes its toxicity to muscle is poorly understood. Here, we show that the nematode C. elegans recapitulates key aspects of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and organization and induces the expression of protective genes, including oxidative stress response. In addition, ethanol exposure causes a fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol-induced mitochondrial fragmentation is dependent on mitochondrial fission factor DRP-1 (dynamin-like protein 1), and its receptor proteins on the mitochondrial outer membrane. Our data indicate that this fragmentation contributes to activation of mitochondrial unfolded protein response (UPR). We also found that robust perpetual mitochondrial UPR activation effectively counters muscle weakness caused by ethanol exposure. Our results strongly suggest that modulation of mitochondrial stress responses provides a mechanism to ameliorate alcohol toxicity and damage to muscle.SignificanceChronic alcohol abuse causes the damage and toxicity to peripheral tissues, including muscle. Alcohol perturbs the structure and function of striated skeletal and cardiac muscles. These toxic effects of alcohol on striated muscles negatively impact morbidity and mortality to alcohol misusers. Here, we demonstrate that the nematode C. elegans also exhibits key features of alcoholic myopathy when exposed to ethanol. Ethanol exposure impairs muscle organization and strength, and induces the expression of genes that cope with alcohol toxicity. Particularly, we find that ethanol toxicity is centered on mitochondria, the power plants of the cell. As an adaptive protective response to mitochondrial dysfunction, ethanol-exposed cells induce global transcriptional reprogramming to restore normal mitochondrial function. Upregulation of this transcriptional reprogramming in C. elegans effectively blocks ethanol-induced muscle weakness, a key feature of alcoholic myopathy. Thus, the modulation of mitochondrial stress responses is a potentially promising therapeutic strategy to ameliorate alcohol toxicity to muscle.

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Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations

Zhang,

Tian,

Majumdar

et al. 2024

Comprehensive Physiology

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Bone marrow adipose tissue (BMAT) is a metabolically and clinically relevant fat depot that exists within bone. Two subtypes of BMAT, regulated and constitutive, reside in hematopoietic‐rich red marrow and fatty yellow marrow, respectively, and exhibit distinct characteristics compared to peripheral fat such as white and brown adipose tissues. Bone marrow adipocytes (BMAds) are evolutionally preserved in most vertebrates, start development after birth and expand throughout life, and originate from unique progenitor populations that control bone formation and hematopoiesis. Mature BMAds also interact closely with other cellular components of the bone marrow niche, serving as a nearby energy reservoir to support the skeletal system, a signaling hub that contributes to both local and systemic homeostasis, and a final fuel reserve for survival during starvation. Though BMAT and bone are often inversely correlated, more BMAT does not always mean less bone, and the prevention of BMAT expansion as a strategy to prevent bone loss remains questionable. BMAT adipogenesis and lipid metabolism are regulated by the nervous systems and a variety of circulating hormones. This contributes to the plasticity of BMAT, including BMAT expansion in common physiological or pathological conditions, and BMAT catabolism under certain extreme circumstances, which are often associated with malnutrition and/or systemic inflammation. Altogether, this article provides a comprehensive overview of the local and systemic functions of BMAT and discusses the regulation and plasticity of this unique adipose tissue depot in health and disease. © 2024 American Physiological Society. Compr Physiol 14:5521‐5579, 2024.

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Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol

Cited by 39 publications

References 126 publications

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations

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