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Title: Enhancing hepatic fatty acid oxidation as a strategy for reversing metabolic disorders programmed by maternal undernutrition during gestation
Author: Torrens, Juana María
Orellana Gavaldà, Josep Maria
Palou, Mariona
Sánchez, Juana
Herrero Rodríguez, Laura
Picó, Catalina
Serra i Cucurull, Dolors
Palou Oliver, Andreu
Keywords: Àcids grassos
Dieta hipocalòrica
Teràpia genètica
Complicacions en l'embaràs
Trastorns del metabolisme
Fatty acids
Low-calorie diet
Gene therapy
Disorders of metabolism
Complications of pregnancy
Issue Date: May-2014
Publisher: Karger
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.
Note: Reproducció del document publicat a:
It is part of: Cellular Physiology and Biochemistry, 2014, vol. 33, num. 5, p. 1498-1515
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ISSN: 1015-8987
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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