Pioglitazone prevents alcohol-induced fatty liver in rats through up-regulation of c-Met
Open accessAbstract
Background & aims Treatment of steatosis is important in preventing development of fibrosis in alcoholic liver diseases. This study aimed to examine if pioglitazone, an antidiabetic reagent serving as a ligand of peroxisome proliferator-activated receptor gamma (PPAR gamma), could prevent alcoholic fatty liver.Methods Rats fed with an ethanol-containing liquid diet were given the reagent at 10 mg/kg per day intragastrically for 6 weeks. Hepatic genes involved in actions of the reagent were mined by transcriptome analyses, and their changes were confirmed by real-time polymerase chain reaction and Western blotting analyses. The direct effects of pioglitazone on primary-cultured hepatocytes were also assessed in vitro.Results Pioglitazone significantly attenuated steatosis and lipid peroxidation elicited by chronic ethanol exposure without altering insulin resistance. Mechanisms for improving effects of the reagent appeared to involve restoration of the ethanol-induced down-regulation of c-Met and up-regulation of stearoyl-CoA desaturase (SCD). Such effects of pioglitazone on the c-Met signaling pathway resulted from its tyrosine phosphorylation and resultant up-regulation of the apolipoprotein B (apoB)-mediated lipid mobilization from hepatocytes through very low-density lipoprotein (VLDL) as well as down-regulation of sterol regulatory element binding protein (SREBP) -1c and SCD levels and a decrease in triglyceride synthesis in the liver.Conclusions Pioglitazone activates c-Met and VLDL-dependent lipid retrieval and suppresses triglyceride synthesis and thereby serves as a potentially useful stratagem to attenuate ethanol-induced hepatic steatosis.
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Several other in vitro and in vivo studies on hepatic stellate cells confirmed the anti-fibrotic potential of synthetic PPAR-γ ligands.
“Several other in vitro [131] and in vivo studies [132,133] on HSCs confirmed the anti-fibrotic potential of synthetic PPAR-γ ligands.”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [133]
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References 40 · Cited by 141
Research works printed but not linked: 3
- Horikoshi H, Yoshioka T, Kawasaki T, Nakamura K, Matsunuma N, Yamaguchi K, Sasahara K. Troglitazone (CS-045), a new an- tidiabetic drug. Annu Rep Sankyo Res Lab 1994;46:1-57.
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- Authors
- Tomita, K., Azuma, T., Kitamura, N., Nishida, J., Tamiya, G., Oka, A., Inokuchi, S., Nishimura, T., Suematsu, M., & Ishii, H.
- Affiliations
- Keio University (JP)
- Tokyo Dental College (JP)
- Tokai University (JP)
- Corresponding author
- Ishii, Hiromasa
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 126
- Issue
- 3
- Pages
- 873-885
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2055628636
- Cited by
- 141
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 6 · 2013: 3 · 2012: 12
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, alcoholic fatty liver, hepatic steatosis, c-Met, PPARγ, stearoyl-CoA desaturase, apolipoprotein B, SREBP-1c, triglyceride synthesis, lipid peroxidation, chronic ethanol exposure, hepatocytes, insulin resistance
- MeSH terms
- Pioglitazone, Alcohol Drinking, Animals, Apolipoproteins B, Cells, Cultured, DNA, DNA-Binding Proteins, Fatty Liver, Alcoholic, Isoenzymes, Liver, Male, Phosphorylation, Stearoyl-CoA Desaturase, Time Factors, Transcription Factors, Tyrosine, Lipid Peroxidation, Up-Regulation, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-met, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, CCAAT-Enhancer-Binding Proteins, Hepatocytes, Thiazolidinediones, Rats, Sterol Regulatory Element Binding Protein 1
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