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Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation

[Image: see text] Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Her...

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Autores principales: Cheng, Kian-Kai, Akasaki, Yuichi, Lecommandeur, Emmanuelle, Lindsay, Ross T., Murfitt, Steven, Walsh, Kenneth, Griffin, Julian L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286153/
https://www.ncbi.nlm.nih.gov/pubmed/25231380
http://dx.doi.org/10.1021/pr500756u
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author Cheng, Kian-Kai
Akasaki, Yuichi
Lecommandeur, Emmanuelle
Lindsay, Ross T.
Murfitt, Steven
Walsh, Kenneth
Griffin, Julian L.
author_facet Cheng, Kian-Kai
Akasaki, Yuichi
Lecommandeur, Emmanuelle
Lindsay, Ross T.
Murfitt, Steven
Walsh, Kenneth
Griffin, Julian L.
author_sort Cheng, Kian-Kai
collection PubMed
description [Image: see text] Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity.
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spelling pubmed-42861532015-09-18 Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation Cheng, Kian-Kai Akasaki, Yuichi Lecommandeur, Emmanuelle Lindsay, Ross T. Murfitt, Steven Walsh, Kenneth Griffin, Julian L. J Proteome Res [Image: see text] Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity. American Chemical Society 2014-09-18 2015-01-02 /pmc/articles/PMC4286153/ /pubmed/25231380 http://dx.doi.org/10.1021/pr500756u Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Cheng, Kian-Kai
Akasaki, Yuichi
Lecommandeur, Emmanuelle
Lindsay, Ross T.
Murfitt, Steven
Walsh, Kenneth
Griffin, Julian L.
Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title_full Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title_fullStr Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title_full_unstemmed Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title_short Metabolomic Analysis of Akt1-Mediated Muscle Hypertrophy in Models of Diet-Induced Obesity and Age-Related Fat Accumulation
title_sort metabolomic analysis of akt1-mediated muscle hypertrophy in models of diet-induced obesity and age-related fat accumulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286153/
https://www.ncbi.nlm.nih.gov/pubmed/25231380
http://dx.doi.org/10.1021/pr500756u
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