Cited by 1,298Liver Disease Diagnosis and TreatmentAdipokines, Inflammation, and Metabolic DiseasesAlcohol Consumption and Health Effects

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The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

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Xu, Aimin, Wang, Yu, Keshaw, Hussila, Xu, Lance Yi, Lam, Karen S.L., Cooper, Garth J.S.·2003·Journal of Clinical Investigation

DOI 10.1172/jci200317797PMC PMC162288

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Abstract

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-α and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.

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Authors: Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S.
Affiliations: University of Auckland (NZ)
University of Hong Kong (HK)
Corresponding author: Xu, Aimin
ORCID: Xu, Aimin
Wang, Yu
Lam, Karen S.L.
Cooper, Garth J.S.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2003-07-01
Volume: 112
Issue: 1
Pages: 91-100
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200317797
PMC: PMC162288
OpenAlex: W2120590109
Cited by: 1,298
References: 68
Citations by year: 2026: 12 · 2025: 15 · 2024: 29 · 2023: 34 · 2022: 34 · 2021: 43 · 2020: 38 · 2019: 35 · 2018: 54 · 2017: 50 · 2016: 50 · 2015: 69 · 2014: 75 · 2013: 59 · 2012: 68
FWCI: 49.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Auckland Medical Research Foundation
University of Hong Kong
Health Research Council of New Zealand
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: adiponectin, alcoholic fatty liver, non-alcoholic fatty liver disease, hepatic steatosis, hepatomegaly, liver inflammation, TNF-α, carnitine palmitoyltransferase 1, hepatic fatty acid oxidation, fatty acid synthesis, acetyl-CoA carboxylase, fatty acid synthase, alanine aminotransferase, ob/ob mice, obesity
MeSH terms: Alanine Transaminase, Animals, Fatty Acids, Fatty Liver, Fatty Liver, Alcoholic, Liver, Male, Mice, Inbred C57BL, Obesity, Morbid, Oxidation-Reduction, Proteins, Recombinant Proteins, Tumor Necrosis Factor-alpha, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin

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The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

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