TY - JOUR
T1 - A review of the role of ethanol-induced adipose tissue dysfunction in alcohol-associated liver disease
AU - Gopal, Thiyagarajan
AU - Ai, Weilun
AU - Casey, Carol A.
AU - Donohue, Terrence M.
AU - Saraswathi, Viswanathan
N1 - Funding Information:
The report was funded by R21 awards from NIH‐National Institute on Alcohol Abuse and Alcoholism (R21‐AA025445 and R21‐AA027367) and a seed grant from Nebraska Research Initiatives. VS is also supported by an R21 award from the NIH‐National Cancer Institute (R21‐CA238953) and a Merit Award from the Department of Veterans Affairs (I01CX002084). This paper is the result of work conducted with the resources and the facilities at the VA‐Nebraska Western Iowa Health Care System, Omaha, Nebraska.
Publisher Copyright:
© 2021 by the Research Society on Alcoholism.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - AT browning
KW - CYP2E1
KW - adipokines
KW - adipose tissue
KW - ethanol
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U2 - 10.1111/acer.14698
DO - 10.1111/acer.14698
M3 - Review article
C2 - 34558087
AN - SCOPUS:85115387382
SN - 0145-6008
VL - 45
SP - 1927
EP - 1939
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 10
ER -