Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing with the growing epidemics of obesity and diabetes. NAFLD encompasses a clinicopathologic spectrum of disease ranging from isolated hepatic steatosis to NASH, which is a more aggressive form of fatty liver disease, to cirrhosis and, finally, hepatocellular carcinoma (HCC). The exact mechanism behind the development of HCC in NASH remains unclear; however, it has been established that hepatic steatosis is the important risk factor in the development of HCC. Metformin has recently drawn attention because of its potential antitumor effect. Here, we investigated the effects of metformin on high-fat diet (HFD)-induced liver tumorigenesis, using a mouse model of NASH and liver tumor. Metformin prevented long-term HFD-induced liver tumorigenesis in C57Bl/6 mice. Of note, metformin failed to protect against liver tumorigenesis in mice that had already begun to develop NAFLD. Metformin improved short-term HFD-induced fat accumulation in the liver, associated with the suppression of adipose tissue inflammation. Collectively, these results suggest that metformin may prevent liver tumorigenesis via suppression of liver fat accumulation in the early stage, before the onset of NAFLD, which seems to be associated with a delay in the development of inflammation of the adipose tissue.
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This epidemiologic evidence has coalesced with experimental work in animals.
“This epidemiologic evidence has coalesced with experimental work in animals(256–263).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [262]
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- Authors
- Tajima, K., Nakamura, A., Shirakawa, J., Togashi, Y., Orime, K., Sato, K., Inoue, H., Kaji, M., Sakamoto, E., Ito, Y., Aoki, K., Nagashima, Y., Atsumi, T., & Terauchi, Y.
- Affiliations
- Hokkaido University (JP)
- Department of Endocrinology and Metabolism,
- Yokohama City University (JP)
- Corresponding author
- Terauchi, Y.
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2013-10-15
- Volume
- 305
- Issue
- 8
- Pages
- E987-E998
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2111215209
- Cited by
- 59
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 10 · 2014: 6 · 2013: 1
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dainippon Sumitomo Pharma
- Japan Society for the Promotion of Science (23591316)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- metformin, hepatocarcinogenesis, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, high-fat diet, hepatocellular carcinoma, hepatic steatosis, adipose tissue inflammation, anticancer activity, C57BL/6 mice
- MeSH terms
- Animals, Fatty Liver, Carcinoma, Hepatocellular, Hypoglycemic Agents, Liver, Liver Neoplasms, Male, Metformin, Mice, Inbred C57BL, Obesity, Random Allocation, Anticarcinogenic Agents, Disease Progression, Lipid Metabolism, Mice, Adipose Tissue, White, Diet, High-Fat, Carcinogenesis, Non-alcoholic Fatty Liver Disease
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