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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)

Cell Physiol Biochem. 2014;33(5):1498-515.

(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.

Abstract

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.

doi: 10.1159/000358714.

Event date: 14/05/2014

Publication date: 25/05/2015