Maria Torrens, JuanaOrellana-Gavalda, Josep MPalou, MarionaSanchez, JuanaHerrero, LauraPicó, CatalinaSerra, DolorsPalou, Andreu2024-07-032024-07-032014Maria Torrens J, Orellana-Gavalda JM, Palou March M, Sánchez J, Herrero L, Pico C, et al. Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation. Cell Physiol Biochem. 2014;33(5):1498-515. Epub 2014 May 14.1015-8987http://hdl.handle.net/20.500.13003/11863http://hdl.handle.net/20.500.12105/19959Background/Aims: Moderate maternal calorie-restriction during gestation programmes offspring for a major propensity to develop metabolic alterations in adulthood. We aimed to assess whether increased hepatic fatty-acid oxidation (FAO), at early ages, by gene transfer of Cpt1am (active mutant of carnitine palmitoyltransferase-1a), may be a strategy for reversing metabolic disturbances associated to maternal calorie-restriction during gestation in rats. Methods: AAV-Gfp (control) and AAV-Cpt1am vectors were administered by tail vein injection in 18-day-old control-pups and the offspring of 20% calorie-restricted rats during gestation (CR). After weaning, animals were fed with normal-fat diet. At the age of 4 months, they were moved to HF-diet and sacrificed at the age of 6 months to collect tissues. Locomotive activity, energy expenditure and blood pressure were measured. Results: Under HF-diet, CR-animals showed higher HOMA-IR, adipocyte diameter and hepatic triglyceride accumulation than controls; these alterations were reverted in Cpt1am-injected animals. In liver, this treatment ameliorated inflammatory state, decreased expression of lipogenesis-related genes and partially restored the decreased expression of leptin-receptor occurring in CR-animals. Treatment also reverted the decreased energy expenditure and the increased blood pressure of CR-animals. Conclusion: Increasing hepatic FAO through AAV-Cpt1am injection at juvenile ages prevents some metabolic disorders associated to gestational maternal calorie-restriction.enghttps://creativecommons.org/licenses/by-nc/3.0/Cpt1aCalorie restrictionGestationGene transferenceLiverMalnutritionPregnancy, AnimalHumansMetabolic DiseasesCarnitine O-PalmitoyltransferaseFatty AcidsFatty LiverPregnancyMaleGenetic TherapyPregnancy ComplicationsRats, WistarFemaleRatsAnimalsOxidation-ReductionPrenatal Exposure Delayed Effectsresearch articleAttribution-NonCommercial 3.0 Unported248548393351498-151510.1159/0003587141421-9778Cellular Physiology and Biochemistryopen accessPreñezAnimalesRatas WistarTerapia GenéticaFemeninoMasculinoDesnutriciónEnfermedades MetabólicasHígado GrasoCarnitina O-PalmitoiltransferasaRatasHumanosÁcidos GrasosComplicaciones del EmbarazoEmbarazoEfectos Tardíos de la Exposición PrenatalOxidación-Reducción2-s2.0-84901334432336493300022L373159366