Alcohol intake aggravates adipose browning and muscle atrophy in cancer-associated cachexia

Wang, Bo; Zhang, Faya; Zhang, Hui; Wang, Zhixiu; Ma, Yu; Zhu, Mei‐Jun; Du, Min

doi:10.18632/oncotarget.22243

Cited by 10 publications

(15 citation statements)

References 54 publications

(72 reference statements)

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“…On the other hand, another study showed that feeding mice a chronic EtOH diet at 6.4% (vol/vol) for 4 week reduced BAT mass, impaired thermogenesis, and induced browning of WAT (Blaner et al, 2017). Further, alcohol-induced AT browning promotes muscle atrophy in cancer-associated cachexia (Wang et al, 2017b). Moreover, increased fatty acid oxidation during thermogenesis may also reduce lipid storage in AT upon EtOH exposure.…”

Section: Alcohol S Timul Ate S Bat Thermog Ene S Is/at B Rowningmentioning

confidence: 99%

A review of the role of ethanol‐induced adipose tissue dysfunction in alcohol‐associated liver disease

Gopal

Casey

et al. 2021

Alcoholism Clin & Exp Res

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Alcohol‐associated liver disease (AALD) encompasses a spectrum of liver diseases that includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis. The adverse effects of alcohol in liver and the mechanisms by which ethanol (EtOH) promotes liver injury are well studied. Although liver is known to be the primary organ affected by EtOH exposure, alcohol's effects on other organs are also known to contribute significantly to the development of liver injury. It is becoming increasingly evident that adipose tissue (AT) is an important site of EtOH action. Both AT storage and secretory functions are altered by EtOH. For example, AT lipolysis, stimulated by EtOH, contributes to chronic alcohol‐induced hepatic steatosis. Adipocytes secrete a wide variety of biologically active molecules known as adipokines. EtOH alters the secretion of these adipokines from AT, which include cytokines and chemokines that exert paracrine effects in liver. In addition, the level of EtOH‐metabolizing enzymes, in particular, CYP2E1, rises in the AT of EtOH‐fed mice, which promotes oxidative stress and/or inflammation in AT. Thus, AT dysfunction characterized by increased AT lipolysis and free fatty acid mobilization and altered secretion of adipokines can contribute to the severity of AALD. Of note, moderate EtOH exposure results in AT browning and activation of brown adipose tissue which, in turn, can promote thermogenesis. In this review article, we discuss the direct effects of EtOH consumption in AT and the mechanisms by which EtOH impacts the functions of AT, which, in turn, increases the severity of AALD in animal models and humans.

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Section: Alcohol S Timul Ate S Bat Thermog Ene S Is/at B Rowningmentioning

confidence: 99%

A review of the role of ethanol‐induced adipose tissue dysfunction in alcohol‐associated liver disease

Gopal

Casey

et al. 2021

Alcoholism Clin & Exp Res

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“…Peroxisome proliferatoractivated receptor γ (PPARγ) (Rosen et al, 2002), PPARγ coactivator 1α (PGC-1α) (Puigserver et al, 1998), PR domain containing 16 (PRDM16) (Seale et al, 2007), and other transcription factors are responsible for UCP1 production in brown and beige adipocytes. Other than that, extracellular stimulations, such as catecholamines (Nguyen et al, 2011), crotamine (Marinovic et al, 2018), prostaglandins (Vegiopoulos et al, 2010), fibroblast growth factor 21 (FGF21) (Dutchak et al, 2012), ZAG (Elattar et al, 2018), Bone morphogenetic proteins (BMPs) (Tseng et al, 2008), and alcohol-retinoic acid axis (Wang et al, 2017), have recently been reported to elevate the browning process and facilitate CAC. During the browning process, beige cells de novo originated from a smooth muscle cell-like lineage and can be converted back to the "white-like" phenotype (Rosenwald et al, 2013;Wang et al, 2013), while PRDM16 (Long et al, 2014) and BMP7 (McDonald et al, 2015) serve as strong stimulators for their differentiation.…”

Section: Browning In Cacmentioning

confidence: 99%

Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia

Sun

Feng

et al. 2020

Front. Cell Dev. Biol.

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Loss of body weight, especially loss of adipose tissue and skeletal muscle weight, characterizes cancer-associated cachexia (CAC). Clinically, therapeutic options for CAC are limited due to the complicated signaling between cancer and other organs. Recent research advances show that adipose tissues play a critical role during thermogenesis, glucose homeostasis, insulin sensitivity, and lipid metabolism. Understanding the adipocyte lipolysis, the formation of beige adipocytes, and the activation of brown adipocytes is vital for novel therapies for metabolic syndromes like CAC. The systemlevel crosstalk between adipose tissue and other organs involves adipocyte lipolysis, white adipose tissue browning, and secreted factors and metabolites. Novel CAC animal models and accumulating molecular signaling knowledge have provided mechanisms that may ultimately be translated into future therapeutic possibilities that benefit CAC patients. This mini review discusses the role of adipose tissue in CAC development, mechanism, and therapy.

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“…Chronic alcohol consumption induces skeletal muscle atrophy in rats (Lang et al, 1999, Lang et al, 2007, Steiner and Lang, 2015, Gritsyna et al, 2017, enhances muscle wasting in SIV infected macaque monkeys (Molina et al, 2008), and promotes sarcopenia in human alcoholics with alcoholic liver disease (Dasarathy et al, 2017). Chronic alcohol consumption also enhances CAC in mice bearing B16BL6 melanoma (Núñez et al, 2002, Zhang et al, 2015a, Wang et al, 2017. However, the underlying molecular mechanism of how alcohol enhances CAC remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Chronic Alcohol Consumption Enhances Skeletal Muscle Wasting in Mice Bearing Cachectic Cancers: The Role of TNFα/Myostatin Axis

Zhang

Modrak

et al. 2019

Alcoholism Clin & Exp Res

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Background: Chronic alcohol consumption enhances cancer-associated cachexia, which is one of the major causes of decreased survival. The precise molecular mechanism of how alcohol consumption enhances cancer-associated cachexia, especially skeletal muscle loss, remains to be elucidated. Methods:We used a mouse model of chronic alcohol consumption, in which 20% (w/v) alcohol was provided as sole drinking fluid, and Lewis lung carcinoma to study the underlying mechanisms. Results:We found that alcohol consumption up regulated the expression of MAFbx, MuRF-1 and LC3 in skeletal muscle, suggesting that alcohol enhanced ubiquitin-mediated proteolysis and LC3-mediated autophagy. Alcohol consumption enhanced phosphorylation of Smad2/3, p38, and ERK, and decreased the phosphorylation of FOXO1. These are the signaling molecules governing protein degradation pathways. Moreover, alcohol consumption slightly up regulated the expression of insulin receptor substrate-1, did not affect PI3K, but decreased the phosphorylation of Akt and mTOR, and down regulated the expression of Raptor and p70S6K, suggesting that alcohol impaired protein synthesis signaling pathway in skeletal muscle of tumor-bearing mice. Alcohol consumption enhanced the expression of myostatin in skeletal muscle, plasma and tumor, but did not affect the expression of myostatin in non-tumor-bearing mice. In TNFα knockout mice, the effects of alcohol-enhanced expression of myostatin and protein degradation-related signaling molecules, and decreased protein synthesis signaling in skeletal muscle were abolished. Consequently, alcohol consumption neither affected cancer-associated cachexia, nor decreased the survival of TNFα KO mice bearing cachectic cancer.

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Alcohol intake aggravates adipose browning and muscle atrophy in cancer-associated cachexia

Cited by 10 publications

References 54 publications

A review of the role of ethanol‐induced adipose tissue dysfunction in alcohol‐associated liver disease

A review of the role of ethanol‐induced adipose tissue dysfunction in alcohol‐associated liver disease

Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia

Chronic Alcohol Consumption Enhances Skeletal Muscle Wasting in Mice Bearing Cachectic Cancers: The Role of TNFα/Myostatin Axis

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