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oai:repisalud.isciii.es:20.500.12105/199592024-11-28T19:55:49Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Maria Torrens, Juana author Orellana-Gavalda, Josep M author Palou, Mariona author Sanchez, Juana author Herrero, Laura author Picó, Catalina author Serra, Dolors author Palou, Andreu author 2014 Background/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. Maria 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. 10.1159/000358714 1421-9778 1015-8987 Cellular Physiology and Biochemistry http://hdl.handle.net/20.500.13003/11863 24854839 L373159366 2-s2.0-84901334432 http://hdl.handle.net/20.500.12105/19959 336493300022 Cpt1a Calorie restriction Gestation Gene transference Liver Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation