Adipose lipolysis is important for ethanol to induce fatty liver in the National Institute on Alcohol Abuse and Alcoholism murine model of chronic and binge ethanol feeding

Abstract

Background and Aims: Alcohol-associated liver disease (ALD) pathologies include steatosis, inflammation, and injury, which may progress to fibrosis, cirrhosis, and cancer. The liver receives ~60% of fatty acids from adipose tissue triglyceride hydrolysis, but the role of this lipolytic pathway in ALD development has not been directly examined in any genetic animal models with selective inactivation of adipose lipolysis.Approach and Results: Using adipose-specific comparative gene identification-58 (CGI-58) knockout (FAT-KO) mice, a model of impaired adipose lipolysis, we show that mice deficient in adipose lipolysis are almost completely protected against ethanol-induced hepatic steatosis and lipid peroxidation when subjected to the National Institute on Alcohol Abuse and

Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review

“…However, steatosis in L02 cells was induced by cotreating the cells with oleic acid and ethanol, which does not reflect pure NAFLD. Nevertheless, these investigations suggest that acute APAP could aggravate steatosis through a direct effect on hepatocytes and not via extrahepatic pathways such as fat mobilization from adipose tissue [ 75 , 76 ].…”

Ethanol and its Nonoxidative Metabolites Promote Acute Liver Injury by Inducing ER Stress, Adipocyte Death, and Lipolysis

“…Because serum levels of FFAs were highly increased after a single ethanol binge, and adipose lipolysis has been shown to promote steatosis, 20 we wondered whether adipose tissue is the source of circulating FFAs through the lipolytic process in the adipose tissues. To test this hypothesis, we performed Western blot analyses of lipolysis-related proteins.…”

“… 17 Chronic alcohol consumption markedly increases adipocyte death 18 and lipolytic activity in murine adipose tissue. 19 , 20 An increase in adipose tissue lipolysis causes the release of nonesterified free fatty acids, providing an extrahepatic source of free fatty acids for accumulation in hepatocytes, causing hepatic steatosis by the esterification process to triglycerides. 21 The role of adipose tissue in binge alcohol consumption and liver injury remains elusive.…”

Letter to the editor: Adipose lipolysis is important for ethanol to induce fatty liver in the NIAAA murine model of chronic and binge ethanol feeding

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To the editor, We followed with interest the report by Mathur et al [1] on adipose lipolysis in mediating ethanol-induced hepatic steatosis and lipid peroxidation, eventually leading to fatty liver. There are some disputes and defects in the experimental model.Firstly, the baseline of mice was different (male aged 8-10 weeks and female aged 10-12 weeks), and the alanine transaminase (ALT) and aspartate transaminase in the adipose-specific Comparative Gene Identification-58 knockout group were significantly higher than those in the wild-type group.

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