Cargando…

Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators

Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal under...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramírez-López, María T., Arco, Rocío, Decara, Juan, Vázquez, Mariam, Rivera, Patricia, Blanco, Rosario Noemi, Alén, Francisco, Gómez de Heras, Raquel, Suárez, Juan, Rodríguez de Fonseca, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187359/
https://www.ncbi.nlm.nih.gov/pubmed/28082878
http://dx.doi.org/10.3389/fnbeh.2016.00241
_version_ 1782486825539993600
author Ramírez-López, María T.
Arco, Rocío
Decara, Juan
Vázquez, Mariam
Rivera, Patricia
Blanco, Rosario Noemi
Alén, Francisco
Gómez de Heras, Raquel
Suárez, Juan
Rodríguez de Fonseca, Fernando
author_facet Ramírez-López, María T.
Arco, Rocío
Decara, Juan
Vázquez, Mariam
Rivera, Patricia
Blanco, Rosario Noemi
Alén, Francisco
Gómez de Heras, Raquel
Suárez, Juan
Rodríguez de Fonseca, Fernando
author_sort Ramírez-López, María T.
collection PubMed
description Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner.
format Online
Article
Text
id pubmed-5187359
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-51873592017-01-12 Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators Ramírez-López, María T. Arco, Rocío Decara, Juan Vázquez, Mariam Rivera, Patricia Blanco, Rosario Noemi Alén, Francisco Gómez de Heras, Raquel Suárez, Juan Rodríguez de Fonseca, Fernando Front Behav Neurosci Neuroscience Maternal malnutrition causes long-lasting alterations in feeding behavior and energy homeostasis in offspring. It is still unknown whether both, the endocannabinoid (eCB) machinery and the lipid metabolism are implicated in long-term adaptive responses to fetal reprogramming caused by maternal undernutrition. We investigated the long-term effects of maternal exposure to a 20% standard diet restriction during preconceptional and gestational periods on the metabolically-relevant tissues hypothalamus, liver, and perirenal fat (PAT) of male and female offspring at adulthood. The adult male offspring from calorie-restricted dams (RC males) exhibited a differential response to the CB1 antagonist AM251 in a chocolate preference test as well as increased body weight, perirenal adiposity, and plasma levels of triglycerides, LDL, VLDL, bilirubin, and leptin. The gene expression of the cannabinoid receptors Cnr1 and Cnr2 was increased in RC male hypothalamus, but a down-expression of most eCBs-metabolizing enzymes (Faah, Daglα, Daglβ, Mgll) and several key regulators of fatty-acid β-oxidation (Cpt1b, Acox1), mitochondrial respiration (Cox4i1), and lipid flux (Pparγ) was found in their PAT. The female offspring from calorie-restricted dams exhibited higher plasma levels of LDL and glucose as well as a reduction in chocolate and caloric intake at post-weaning periods in the feeding tests. Their liver showed a decreased gene expression of Cnr1, Pparα, Pparγ, the eCBs-degrading enzymes Faah and Mgll, the de novo lipogenic enzymes Acaca and Fasn, and the liver-specific cholesterol biosynthesis regulators Insig1 and Hmgcr. Our results suggest that the long-lasting adaptive responses to maternal caloric restriction affected cannabinoid-regulated mechanisms involved in feeding behavior, adipose β-oxidation, and hepatic lipid and cholesterol biosynthesis in a sex-dependent manner. Frontiers Media S.A. 2016-12-27 /pmc/articles/PMC5187359/ /pubmed/28082878 http://dx.doi.org/10.3389/fnbeh.2016.00241 Text en Copyright © 2016 Ramírez-López, Arco, Decara, Vázquez, Rivera, Blanco, Alén, Gómez de Heras, Suárez and Rodríguez de Fonseca. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Ramírez-López, María T.
Arco, Rocío
Decara, Juan
Vázquez, Mariam
Rivera, Patricia
Blanco, Rosario Noemi
Alén, Francisco
Gómez de Heras, Raquel
Suárez, Juan
Rodríguez de Fonseca, Fernando
Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title_full Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title_fullStr Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title_full_unstemmed Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title_short Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators
title_sort long-term effects of prenatal exposure to undernutrition on cannabinoid receptor-related behaviors: sex and tissue-specific alterations in the mrna expression of cannabinoid receptors and lipid metabolic regulators
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187359/
https://www.ncbi.nlm.nih.gov/pubmed/28082878
http://dx.doi.org/10.3389/fnbeh.2016.00241
work_keys_str_mv AT ramirezlopezmariat longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT arcorocio longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT decarajuan longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT vazquezmariam longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT riverapatricia longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT blancorosarionoemi longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT alenfrancisco longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT gomezdeherasraquel longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT suarezjuan longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators
AT rodriguezdefonsecafernando longtermeffectsofprenatalexposuretoundernutritiononcannabinoidreceptorrelatedbehaviorssexandtissuespecificalterationsinthemrnaexpressionofcannabinoidreceptorsandlipidmetabolicregulators