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Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice

Caloric restriction (CR) has been shown to extend longevity and protect brain function in aging. However, the effects of CR in young adult mice remain largely unexplored. In addition to the fundamental, long-term changes, recent studies demonstrate that CR has a significant impact on transient, post...

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Autores principales: Yanckello, Lucille M., Young, Lyndsay E. A., Hoffman, Jared D., Mohney, Robert P., Keaton, Mignon A., Abner, Erin, Lin, Ai-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582370/
https://www.ncbi.nlm.nih.gov/pubmed/31249833
http://dx.doi.org/10.3389/fnut.2019.00090
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author Yanckello, Lucille M.
Young, Lyndsay E. A.
Hoffman, Jared D.
Mohney, Robert P.
Keaton, Mignon A.
Abner, Erin
Lin, Ai-Ling
author_facet Yanckello, Lucille M.
Young, Lyndsay E. A.
Hoffman, Jared D.
Mohney, Robert P.
Keaton, Mignon A.
Abner, Erin
Lin, Ai-Ling
author_sort Yanckello, Lucille M.
collection PubMed
description Caloric restriction (CR) has been shown to extend longevity and protect brain function in aging. However, the effects of CR in young adult mice remain largely unexplored. In addition to the fundamental, long-term changes, recent studies demonstrate that CR has a significant impact on transient, postprandial metabolic flexibility and turnover compared to control groups. The goal of this study was to identify the brain metabolic changes at a transient (2 h) and steady (6 h) postprandial state in young mice (5–6 months of age) fed with CR or ad libitum (AL; free eating). Using metabolomics profiling, we show that CR mice had significantly higher levels of neurotransmitters (e.g., glutamate, N-acetylglutamate), neuronal integrity markers (e.g., NAA and NAAG), essential fatty acids (e.g., DHA and DPA), and biochemicals associated carnitine metabolism (related to reduced oxidative stress and inflammation) in the cerebral cortex and hippocampus at 2-h. These biochemicals remained at high levels at the 6-h postprandial time-point. The AL mice did not show the similar increases in essential fatty acid and carnitine metabolism until the 6-h time-point, and failed to show increases in neurotransmitters and neuronal integrity markers at any time-point. On the other hand, metabolites related to glucose utilization—glycolysis and pentose phosphate pathway (PPP)—were low in the CR mice throughout the 6-h period and significantly increased at the 6-h time-point in the AL mice. Our findings suggest that CR induces distinct postprandial responses in metabolites that are essential to maintain brain functions. CR mice produced higher levels of essential brain metabolites in a shorter period after a meal and sustained the levels for an extended period, while maintaining a lower level of glucose utilization. These early brain metabolism changes in the CR mice might play a critical role for neuroprotection in aging. Understanding the interplay between dietary intervention and postprandial metabolic responses from an early age may have profound implications for impeding brain aging and reducing risk for neurodegenerative disorders.
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spelling pubmed-65823702019-06-27 Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice Yanckello, Lucille M. Young, Lyndsay E. A. Hoffman, Jared D. Mohney, Robert P. Keaton, Mignon A. Abner, Erin Lin, Ai-Ling Front Nutr Nutrition Caloric restriction (CR) has been shown to extend longevity and protect brain function in aging. However, the effects of CR in young adult mice remain largely unexplored. In addition to the fundamental, long-term changes, recent studies demonstrate that CR has a significant impact on transient, postprandial metabolic flexibility and turnover compared to control groups. The goal of this study was to identify the brain metabolic changes at a transient (2 h) and steady (6 h) postprandial state in young mice (5–6 months of age) fed with CR or ad libitum (AL; free eating). Using metabolomics profiling, we show that CR mice had significantly higher levels of neurotransmitters (e.g., glutamate, N-acetylglutamate), neuronal integrity markers (e.g., NAA and NAAG), essential fatty acids (e.g., DHA and DPA), and biochemicals associated carnitine metabolism (related to reduced oxidative stress and inflammation) in the cerebral cortex and hippocampus at 2-h. These biochemicals remained at high levels at the 6-h postprandial time-point. The AL mice did not show the similar increases in essential fatty acid and carnitine metabolism until the 6-h time-point, and failed to show increases in neurotransmitters and neuronal integrity markers at any time-point. On the other hand, metabolites related to glucose utilization—glycolysis and pentose phosphate pathway (PPP)—were low in the CR mice throughout the 6-h period and significantly increased at the 6-h time-point in the AL mice. Our findings suggest that CR induces distinct postprandial responses in metabolites that are essential to maintain brain functions. CR mice produced higher levels of essential brain metabolites in a shorter period after a meal and sustained the levels for an extended period, while maintaining a lower level of glucose utilization. These early brain metabolism changes in the CR mice might play a critical role for neuroprotection in aging. Understanding the interplay between dietary intervention and postprandial metabolic responses from an early age may have profound implications for impeding brain aging and reducing risk for neurodegenerative disorders. Frontiers Media S.A. 2019-06-12 /pmc/articles/PMC6582370/ /pubmed/31249833 http://dx.doi.org/10.3389/fnut.2019.00090 Text en Copyright © 2019 Yanckello, Young, Hoffman, Mohney, Keaton, Abner and Lin. 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 Nutrition
Yanckello, Lucille M.
Young, Lyndsay E. A.
Hoffman, Jared D.
Mohney, Robert P.
Keaton, Mignon A.
Abner, Erin
Lin, Ai-Ling
Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title_full Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title_fullStr Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title_full_unstemmed Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title_short Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites in Young Adult Mice
title_sort caloric restriction alters postprandial responses of essential brain metabolites in young adult mice
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582370/
https://www.ncbi.nlm.nih.gov/pubmed/31249833
http://dx.doi.org/10.3389/fnut.2019.00090
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