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Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)

BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a na...

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Autores principales: Zhang, Xue-Ying, Zhang, Qiang, Wang, De-Hua
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102676/
https://www.ncbi.nlm.nih.gov/pubmed/21637839
http://dx.doi.org/10.1371/journal.pone.0019913
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author Zhang, Xue-Ying
Zhang, Qiang
Wang, De-Hua
author_facet Zhang, Xue-Ying
Zhang, Qiang
Wang, De-Hua
author_sort Zhang, Xue-Ying
collection PubMed
description BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China. METHODOLOGY/PRINCIPAL FINDINGS: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.
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spelling pubmed-31026762011-06-02 Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii) Zhang, Xue-Ying Zhang, Qiang Wang, De-Hua PLoS One Research Article BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China. METHODOLOGY/PRINCIPAL FINDINGS: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood. Public Library of Science 2011-05-26 /pmc/articles/PMC3102676/ /pubmed/21637839 http://dx.doi.org/10.1371/journal.pone.0019913 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Xue-Ying
Zhang, Qiang
Wang, De-Hua
Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title_full Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title_fullStr Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title_full_unstemmed Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title_short Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)
title_sort litter size variation in hypothalamic gene expression determines adult metabolic phenotype in brandt's voles (lasiopodomys brandtii)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102676/
https://www.ncbi.nlm.nih.gov/pubmed/21637839
http://dx.doi.org/10.1371/journal.pone.0019913
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