Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation

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 carn...

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Main Authors: Juana María Torrens, Josep M. Orellana-Gavaldà, Mariona Palou, Juana Sánchez, Laura Herrero, Catalina Picó, Dolors Serra, Andreu Palou
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2014-05-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/358714
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author Juana María Torrens
Josep M. Orellana-Gavaldà
Mariona Palou
Juana Sánchez
Laura Herrero
Catalina Picó
Dolors Serra
Andreu Palou
author_facet Juana María Torrens
Josep M. Orellana-Gavaldà
Mariona Palou
Juana Sánchez
Laura Herrero
Catalina Picó
Dolors Serra
Andreu Palou
author_sort Juana María Torrens
collection DOAJ
description 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.
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spelling doaj.art-686b1c0833de435bb6837646124bde502022-12-22T01:50:04ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-05-013351498151510.1159/000358714358714Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During GestationJuana María TorrensJosep M. Orellana-GavaldàMariona PalouJuana SánchezLaura HerreroCatalina PicóDolors SerraAndreu PalouBackground/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.http://www.karger.com/Article/FullText/358714Cpt1aCalorie restrictionGestationGene transferenceLiver
spellingShingle Juana María Torrens
Josep M. Orellana-Gavaldà
Mariona Palou
Juana Sánchez
Laura Herrero
Catalina Picó
Dolors Serra
Andreu Palou
Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
Cellular Physiology and Biochemistry
Cpt1a
Calorie restriction
Gestation
Gene transference
Liver
title Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
title_full Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
title_fullStr Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
title_full_unstemmed Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
title_short Enhancing Hepatic Fatty Acid Oxidation as a Strategy for Reversing Metabolic Disorders Programmed by Maternal Undernutrition During Gestation
title_sort enhancing hepatic fatty acid oxidation as a strategy for reversing metabolic disorders programmed by maternal undernutrition during gestation
topic Cpt1a
Calorie restriction
Gestation
Gene transference
Liver
url http://www.karger.com/Article/FullText/358714
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