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Oxidation of Hepatic Carnitine Palmitoyl Transferase-I (CPT-I) Impairs Fatty Acid Beta-Oxidation in Rats Fed a Methionine-Choline Deficient Diet
Open accessAbstract
There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2) and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.
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“In this study, a NASH rat model fed a methionine-choline-deficient diet had a notable reduction in CPT1A activity and mitochondrial FAO despite increased CPT1A mRNA expression.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [150]
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“The formation of a 4-hydroxynonenal-CPT1 adduct caused by lipid peroxidation as a consequence of ROS overproduction is the main cause of impaired FAO and lipid removal from hepatocytes.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [150]
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Metadata
- Authors
- Serviddio, G., Giudetti, A. M., Bellanti, F., Priore, P., Rollo, T., Tamborra, R., Siculella, L., Vendemiale, G., Altomare, E., & Gnoni, G. V.
- Affiliations
- University of Foggia (IT)
- University of Salento (IT)
- Corresponding author
- Gnoni, Gabriele V.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-09-01
- Volume
- 6
- Issue
- 9
- Pages
- e24084
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3164715
- OpenAlex
- W2007759293
- Cited by
- 128
- References
- 36
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 7 · 2015: 14 · 2014: 9 · 2013: 9 · 2012: 6
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- AIRUS (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- carnitine palmitoyltransferase 1, fatty acid beta-oxidation, nonalcoholic steatohepatitis, methionine-choline-deficient diet, mitochondrial dysfunction, hepatocytes, liver mitochondria, post-translational modification, ketone synthesis, high-fat diet
- MeSH terms
- Acetyl-CoA Carboxylase, Animals, Blood Glucose, Carnitine O-Palmitoyltransferase, Cell Membrane Permeability, Choline, Diet, Fatty Acids, Feeding Behavior, Liver, Male, Malonyl Coenzyme A, Methionine, Mitochondria, Liver, Oxidation-Reduction, RNA, Messenger, 3-Hydroxyacyl CoA Dehydrogenases, Gene Expression Regulation, Enzymologic, Rats, Wistar, Palmitic Acid, Hepatocytes, Mitochondrial Membranes, Rats, Enzyme Assays
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