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http://hdl.handle.net/2445/168921
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DC Field | Value | Language |
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dc.contributor.author | Orellana Gavaldà, Josep Maria | - |
dc.contributor.author | Herrero Rodríguez, Laura | - |
dc.contributor.author | Malandrino, Maria Ida | - |
dc.contributor.author | Pañeda, Astrid | - |
dc.contributor.author | Rodríguez-Peña, Maria Sol | - |
dc.contributor.author | Petry, Harald | - |
dc.contributor.author | Asins Muñoz, Guillermina | - |
dc.contributor.author | Van Deventer, Sander | - |
dc.contributor.author | Hegardt, Fausto | - |
dc.contributor.author | Serra i Cucurull, Dolors | - |
dc.date.accessioned | 2020-07-17T07:43:01Z | - |
dc.date.available | 2020-07-17T07:43:01Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/2445/168921 | - |
dc.description.abstract | Obesity-induced insulin resistance is associated with both ectopic lipid deposition and chronic, low-grade adipose tissue inflammation. Despite their excess fat, obese individuals show lower fatty-acid oxidation (FAO) rates. This has raised the question of whether burning off the excess fat could improve the obese metabolic phenotype. Here we used human-safe nonimmunoreactive adeno-associated viruses (AAV) to mediate long-term hepatic gene transfer of carnitine palmitoyltransferase 1A (CPT1A), the key enzyme in fatty-acid β-oxidation, or its permanently active mutant form CPT1AM, to high-fat diet-treated and genetically obese mice. High-fat diet CPT1A- and, to a greater extent, CPT1AM-expressing mice showed an enhanced hepatic FAO which resulted in increased production of CO(2) , adenosine triphosphate, and ketone bodies. Notably, the increase in hepatic FAO not only reduced liver triacylglyceride content, inflammation, and reactive oxygen species levels but also systemically affected a decrease in epididymal adipose tissue weight and inflammation and improved insulin signaling in liver, adipose tissue, and muscle. Obesity-induced weight gain, increase in fasting blood glucose and insulin levels, and augmented expression of gluconeogenic genes were restored to normal only 3 months after AAV treatment. Thus, CPT1A- and, to a greater extent, CPT1AM-expressing mice were protected against obesity-induced weight gain, hepatic steatosis, diabetes, and obesity-induced insulin resistance. In addition, genetically obese db/db mice that expressed CPT1AM showed reduced glucose and insulin levels and liver steatosis. Conclusion: A chronic increase in liver FAO improves the obese metabolic phenotype, which indicates that AAV-mediated CPT1A expression could be a potential molecular therapy for obesity and diabetes. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Wiley | - |
dc.relation.isformatof | Versió postprint del document publicat a: http://www.ncbi.nlm.nih.gov/pubmed/21520198 | - |
dc.relation.ispartof | Hepatology, 2011, vol. 53, p. 821-832 | - |
dc.rights | (c) American Association for the Study of Liver Diseases, 2011 | - |
dc.source | Articles publicats en revistes (Bioquímica i Fisiologia) | - |
dc.subject.classification | Obesitat | - |
dc.subject.classification | Diabetis | - |
dc.subject.classification | Àcids grassos | - |
dc.subject.classification | Malalties del fetge | - |
dc.subject.other | Obesity | - |
dc.subject.other | Diabetes | - |
dc.subject.other | Fatty acids | - |
dc.subject.other | Liver diseases | - |
dc.title | Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 597331 | - |
dc.date.updated | 2020-07-17T07:43:01Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) |
Files in This Item:
File | Description | Size | Format | |
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597331.pdf | 850.6 kB | Adobe PDF | View/Open |
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