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Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates
Maternal obesity and consumption of a high-fat diet (HFD) during pregnancy has a negative impact on offspring, including an increased risk for the development of obesity in adolescence. The mechanism for this transferred metabolic risk is unclear, but many studies have focused on the brain due to it...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143816/ https://www.ncbi.nlm.nih.gov/pubmed/30258403 http://dx.doi.org/10.3389/fendo.2018.00508 |
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author | True, Cadence Arik, Anam Lindsley, Sarah Kirigiti, Melissa Sullivan, Elinor Kievit, Paul |
author_facet | True, Cadence Arik, Anam Lindsley, Sarah Kirigiti, Melissa Sullivan, Elinor Kievit, Paul |
author_sort | True, Cadence |
collection | PubMed |
description | Maternal obesity and consumption of a high-fat diet (HFD) during pregnancy has a negative impact on offspring, including an increased risk for the development of obesity in adolescence. The mechanism for this transferred metabolic risk is unclear, but many studies have focused on the brain due to its important role in appetite and body-weight regulation. Two main pathways regulate appetite in the brain; homeostatic regulation that occurs predominantly in hypothalamic circuits and hedonic regulation of feeding that occurs via dopaminergic pathways. The current proposal examined the impact of early HFD exposure on the dopaminergic control of hedonic feeding pathways in a translational nonhuman primate model. Japanese macaque offspring from mothers consuming a control (CTR) or HFD were weaned onto control or HFD at an average 8 months of age yielding four groups: maternal and post-weaning control diet (mCTRpCTR), maternal control diet and post-weaning HFD (mCTRpHFD), maternal HFD and post-weaning control diet (mHFDpCTR) and maternal and post-weaning HFD (mHFDpHFD). Brains from 13-month-old offspring were evaluated for expression of neuropeptides that regulate dopaminergic pathways including orexin, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), and tyrosine hydroxylase expression in the ventral tegmental area (VTA). Orexin cell numbers in the LH were significantly increased in animals exposed to a post-weaning HFD, while no difference was observed for orexin mRNA content or MCH cell numbers. Orexin fiber projections to the rostral VTA were significantly reduced in mCTRpHFD, mHFDpCTR, and mHFDpHFD groups, but these differences were not significant in the caudal VTA. There was no difference in the percentage of dopamine neurons receiving close appositions from orexin fibers in either the rostral or caudal VTA, nor was there any difference between groups in the number of orexin contacts per TH cell. In conclusion, the current study finds that prolonged early exposure to HFD during the in utero and postnatal period causes alterations at several levels in the dopaminergic circuits regulating reward. |
format | Online Article Text |
id | pubmed-6143816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61438162018-09-26 Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates True, Cadence Arik, Anam Lindsley, Sarah Kirigiti, Melissa Sullivan, Elinor Kievit, Paul Front Endocrinol (Lausanne) Endocrinology Maternal obesity and consumption of a high-fat diet (HFD) during pregnancy has a negative impact on offspring, including an increased risk for the development of obesity in adolescence. The mechanism for this transferred metabolic risk is unclear, but many studies have focused on the brain due to its important role in appetite and body-weight regulation. Two main pathways regulate appetite in the brain; homeostatic regulation that occurs predominantly in hypothalamic circuits and hedonic regulation of feeding that occurs via dopaminergic pathways. The current proposal examined the impact of early HFD exposure on the dopaminergic control of hedonic feeding pathways in a translational nonhuman primate model. Japanese macaque offspring from mothers consuming a control (CTR) or HFD were weaned onto control or HFD at an average 8 months of age yielding four groups: maternal and post-weaning control diet (mCTRpCTR), maternal control diet and post-weaning HFD (mCTRpHFD), maternal HFD and post-weaning control diet (mHFDpCTR) and maternal and post-weaning HFD (mHFDpHFD). Brains from 13-month-old offspring were evaluated for expression of neuropeptides that regulate dopaminergic pathways including orexin, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), and tyrosine hydroxylase expression in the ventral tegmental area (VTA). Orexin cell numbers in the LH were significantly increased in animals exposed to a post-weaning HFD, while no difference was observed for orexin mRNA content or MCH cell numbers. Orexin fiber projections to the rostral VTA were significantly reduced in mCTRpHFD, mHFDpCTR, and mHFDpHFD groups, but these differences were not significant in the caudal VTA. There was no difference in the percentage of dopamine neurons receiving close appositions from orexin fibers in either the rostral or caudal VTA, nor was there any difference between groups in the number of orexin contacts per TH cell. In conclusion, the current study finds that prolonged early exposure to HFD during the in utero and postnatal period causes alterations at several levels in the dopaminergic circuits regulating reward. Frontiers Media S.A. 2018-09-10 /pmc/articles/PMC6143816/ /pubmed/30258403 http://dx.doi.org/10.3389/fendo.2018.00508 Text en Copyright © 2018 True, Arik, Lindsley, Kirigiti, Sullivan and Kievit. 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) and the copyright owner(s) 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 | Endocrinology True, Cadence Arik, Anam Lindsley, Sarah Kirigiti, Melissa Sullivan, Elinor Kievit, Paul Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title | Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title_full | Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title_fullStr | Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title_full_unstemmed | Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title_short | Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates |
title_sort | early high-fat diet exposure causes dysregulation of the orexin and dopamine neuronal populations in nonhuman primates |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143816/ https://www.ncbi.nlm.nih.gov/pubmed/30258403 http://dx.doi.org/10.3389/fendo.2018.00508 |
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