Torrens J.M. (1), Orellana-Gavaldà J.M. (2), Palou M. (1), Sánchez J. (1), Herrero L. (2), Picó C. (1), Serra D. (2), Palou A. (1)
(1) Laboratory of Molecular Biology, Nutrition, and Biotechnology (Nutrigenomics), University of the Balearic Islands and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Balearic Islands; and (2) Department of Biochemistry and Molecular Biology, Facultat de Farmàcia, Universitat de Barcelona; Institut de Biomedicina de la Universitat de Barcelona (IBUB); and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain.
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.
Event date: 14/05/2014
Publication date: 25/05/2015