Fibroblast Growth Factor 19 Treatment Ameliorates Disruption of Hepatic Lipid Metabolism in Farnesoid X Receptor (Fxr)-Null Mice
Open accessAbstract
Human fibroblast growth factor 19 (FGF19) is an enterohepatic hormone that is involved in the regulation of hepatic metabolism of bile acids, lipids, and glucose. Farnesoid X receptor (Fxr)-null mice exhibit steatosis-like symptoms, showing higher hepatic lipid levels than with the wild-type mice. We investigated the influence of FGF19 treatment on hepatic lipogenesis in Fxr-null mice. Recombinant FGF19 treatment (400 µg/kg/d) for 3 d prevented the accumulation of lipid droplets and decreased serum alanine aminotransferase activity and hepatic lipid levels, including those of triglycerides and free fatty acids. The treatment significantly decreased the hepatic mRNA levels of acetyl-CoA carboxylase 1 (Acc1), Cd36, and sterol regulatory element-binding protein-1c (Srebp-1c) as well as those of acetyl-CoA carboxylase 2 (Acc2), stearoyl CoA desaturase 1 (Scd1), and Cyp7a1. FGF19 treatment (4 µg/kg/d) for 3 d also decreased the hepatic free fatty acid levels and mRNA levels of Acc1, Cd36, and Srebp-1c. These results indicate that FGF19-mediated signaling ameliorates disrupted hepatic lipogenesis in Fxr-null mice.
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The gut microbiota can reduce levels of tauro-beta-muricholic acid (T-βMCA), a naturally occurring FXR antagonist, which subsequently inhibits CYP7A1 by activating FXR-FGF15 signaling and ultimately regulating bile acid metabolism in the liver.
“Sayin et al. found that the gut microbiota can reduce the levels of tauro-beta-muricholic acid (T-βMCA), a naturally occurring FXR antagonist. This subsequently inhibits cholesterol 7a-hydroxylase (CYP7A1), the rate-limiting enzyme in BA synthesis, by activating FXR-FGF15 signaling and ultimately regulating BA metabolism in the liver (5, 11).”
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References 33 · Cited by 77
Research works printed but not linked: 1
- Zhang Y., Lee F. Y., Barrera G., Lee H., Vales C., Gonzalez F. J., Will- son T. M., Edwards P. A., Proc. Natl. Acad. Sci. U.S.A., 103, 1006- 1011 (2006).
- Authors
- Miyata, M., Sakaida, Y., Matsuzawa, H., Yoshinari, K., & Yamazoe, Y.
- Affiliations
- Tohoku University (JP)
- Venue
- Biological and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2011
- Volume
- 34
- Issue
- 12
- Pages
- 1885-1889
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2040086341
- Cited by
- 77
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 6 · 2013: 5 · 2012: 4
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (21390039, 20590137)
- Yakult Bio-Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- FGF19, farnesoid X receptor, hepatic steatosis, hepatic lipogenesis, bile acid metabolism, lipid droplets, acetyl-CoA carboxylase, stearoyl-CoA desaturase 1, SREBP-1c, CYP7A1, CD36, triglycerides, free fatty acids
- MeSH terms
- Receptor, Farnesoid X-Activated, Alanine Transaminase, Alkaline Phosphatase, Animals, Female, Fibroblast Growth Factors, Liver, Recombinant Proteins, RNA, Messenger, Gene Expression, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Lipid Metabolism, Mice
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