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Licensed Unlicensed Requires Authentication Published by De Gruyter February 28, 2019

The effects of dietary methionine restriction on the function and metabolic reprogramming in the liver and brain – implications for longevity

Dušan Mladenović, Tatjana Radosavljević, Dragan Hrnčić, Aleksandra Rasic-Markovic and Olivera Stanojlović

Abstract

Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulation of protein function and methylation reactions. Dietary methionine restriction (0.12–0.17% methionine in food) extends the life span of various animal species and delays the onset of aging-associated diseases and cancers. In the liver, methionine restriction attenuates steatosis and delays the development of non-alcoholic steatohepatitis due to antioxidative action and metabolic reprogramming. The limited intake of methionine stimulates the fatty acid oxidation in the liver and the export of lipoproteins as well as inhibits de novo lipogenesis. These effects are mediated by various signaling pathways and effector molecules, including sirtuins, growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding proteins, adenosine monophosphate-dependent kinase and general control nonderepressible 2 pathway. Additionally, methionine restriction stimulates the synthesis of fibroblast growth factor-21 in the liver, which increases the insulin sensitivity of peripheral tissues. In the brain, methionine restriction delays the onset of neurodegenerative diseases and increases the resistance to various forms of stress through antioxidative effects and alterations in lipid composition. This review aimed to summarize the morphological, functional and molecular changes in the liver and brain caused by the methionine restriction, with possible implications in the prolongation of maximal life span.

Funding source: Ministry of Education, Science and Technological Development of Serbia

Award Identifier / Grant number: 175032

Funding statement: This work was supported by the Ministry of Education, Science and Technological Development of Serbia [Grant No 175032].

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Received: 2018-07-19
Accepted: 2018-10-26
Published Online: 2019-02-28
Published in Print: 2019-07-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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