The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice
Open accessAbstract
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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Adiponectin administration decreases IHTG, increases hepatic insulin sensitivity, and reverses obesity-related skeletal muscle insulin resistance.
“Adiponectin administration decreases IHTG (35), increases hepatic insulin sensitivity (36), and reverses obesity-related skeletal muscle insulin resistance (37).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [35]
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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
- Venue
- Journal of Clinical Investigation
- Published
- 2003-07-01
- Volume
- 112
- Issue
- 1
- Pages
- 91-100
- ISSN
- 0021-9738 (ISSN-L)
- 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 › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Epidemiology › 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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