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Metabolomic analysis of Akt1-mediated muscle hypertrophy in models of diet-induced obesity and age-related fat accumulation

Cheng, Kian Kai and Akasaki, Yuichi and Lecommandeur, Emmanuell and Lindsay, Ross T. and Murfitt, Steven A. and Walsh, Kenneth and Griffin, Julian L. (2014) Metabolomic analysis of Akt1-mediated muscle hypertrophy in models of diet-induced obesity and age-related fat accumulation. Journal of Proteome Research, 14 (1). pp. 342-352. ISSN 1535-3893

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Official URL: http://dx.doi.org/10.1021/pr500756u

Abstract

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

Item Type:Article
Uncontrolled Keywords:metabonomics, obesity, protein kinase B, type 2 diabetes
Subjects:T Technology > TP Chemical technology
Divisions:Chemical Engineering
ID Code:54085
Deposited By: Siti Nor Hashidah Zakaria
Deposited On:05 Apr 2016 06:59
Last Modified:28 Jul 2018 06:26

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