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Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice

Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1...

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Autores principales: Li, Ge, Kohorst, John J., Zhang, Wenjuan, Laritsky, Eleonora, Kunde-Ramamoorthy, Govindarajan, Baker, Maria S., Fiorotto, Marta L., Waterland, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717861/
https://www.ncbi.nlm.nih.gov/pubmed/23545705
http://dx.doi.org/10.2337/db12-1306
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author Li, Ge
Kohorst, John J.
Zhang, Wenjuan
Laritsky, Eleonora
Kunde-Ramamoorthy, Govindarajan
Baker, Maria S.
Fiorotto, Marta L.
Waterland, Robert A.
author_facet Li, Ge
Kohorst, John J.
Zhang, Wenjuan
Laritsky, Eleonora
Kunde-Ramamoorthy, Govindarajan
Baker, Maria S.
Fiorotto, Marta L.
Waterland, Robert A.
author_sort Li, Ge
collection PubMed
description Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1 (P1), mice were fostered in control (C) or small litters (SL). SL mice had increased body weight and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed metabolic studies indicated that female adult SL mice have decreased physical activity and energy expenditure but not increased food intake. Genome-scale DNA methylation profiling identified extensive changes in hypothalamic DNA methylation during the suckling period, suggesting that it is a critical period for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice exhibited subtle and sex-specific changes in hypothalamic DNA methylation that persisted from early life to adulthood, providing a potential mechanistic basis for the sustained physiological effects. Expression profiling in adult hypothalamus likewise provided evidence of widespread sex-specific alterations in gene expression. Together, our data indicate that early postnatal overnutrition leads to a reduction in spontaneous physical activity and energy expenditure in females and suggest that early postnatal life is a critical period during which nutrition can affect hypothalamic developmental epigenetics.
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spelling pubmed-37178612014-08-01 Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice Li, Ge Kohorst, John J. Zhang, Wenjuan Laritsky, Eleonora Kunde-Ramamoorthy, Govindarajan Baker, Maria S. Fiorotto, Marta L. Waterland, Robert A. Diabetes Original Research Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1 (P1), mice were fostered in control (C) or small litters (SL). SL mice had increased body weight and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed metabolic studies indicated that female adult SL mice have decreased physical activity and energy expenditure but not increased food intake. Genome-scale DNA methylation profiling identified extensive changes in hypothalamic DNA methylation during the suckling period, suggesting that it is a critical period for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice exhibited subtle and sex-specific changes in hypothalamic DNA methylation that persisted from early life to adulthood, providing a potential mechanistic basis for the sustained physiological effects. Expression profiling in adult hypothalamus likewise provided evidence of widespread sex-specific alterations in gene expression. Together, our data indicate that early postnatal overnutrition leads to a reduction in spontaneous physical activity and energy expenditure in females and suggest that early postnatal life is a critical period during which nutrition can affect hypothalamic developmental epigenetics. American Diabetes Association 2013-08 2013-07-17 /pmc/articles/PMC3717861/ /pubmed/23545705 http://dx.doi.org/10.2337/db12-1306 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Li, Ge
Kohorst, John J.
Zhang, Wenjuan
Laritsky, Eleonora
Kunde-Ramamoorthy, Govindarajan
Baker, Maria S.
Fiorotto, Marta L.
Waterland, Robert A.
Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title_full Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title_fullStr Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title_full_unstemmed Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title_short Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice
title_sort early postnatal nutrition determines adult physical activity and energy expenditure in female mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717861/
https://www.ncbi.nlm.nih.gov/pubmed/23545705
http://dx.doi.org/10.2337/db12-1306
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