Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice

Emma K Lees; Ruth Banks; Chelsea Cook; Sophie Hill; Nicola Morrice; Louise Grant; Mirela Delibegovic; Nimesh Mody

doi:10.1038/s41598-017-10381-3

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice

Emma K Lees, Ruth Banks, Chelsea Cook, Sophie Hill, Nicola Morrice, Louise Grant, Mirela Delibegovic, Nimesh Mody

Liverpool Hope University

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

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Abstract

The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.

Original language	English
Article number	9977
Pages (from-to)	1-10
Number of pages	10
Journal	Scientific Reports
Volume	7
Early online date	30 Aug 2017
DOIs	https://doi.org/10.1038/s41598-017-10381-3
Publication status	Published - 2017

Bibliographical note

EKL was the recipient of a BBSRC postgraduate studentship. This work was funded by Tenovus Scotland project grant to MD and NM (G13/07) and BBSRC DTG. MD is also supported by the British Heart Foundation (PG/09/048/27675, PG/11/8/28703 and PG/14/43/30889) and Diabetes UK (14/0004853). NM is funded by British Heart Foundation (PG/16/90/32518).

Keywords

molecular biology
obesity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-017-10381-3Licence: CC BY

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL6J mice
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Final published version, 2.03 MBLicence: CC BY

Mirela Delibegovic
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Professor in Diabetes Physiology and Signalling
- School of Medicine, Medical Sciences & Nutrition, Cardiometabolic Disease
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Academic

Cite this

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title = "Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice",

abstract = "The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.",

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AU - Lees, Emma K

AU - Banks, Ruth

AU - Cook, Chelsea

AU - Hill, Sophie

AU - Morrice, Nicola

AU - Grant, Louise

AU - Delibegovic, Mirela

AU - Mody, Nimesh

N1 - EKL was the recipient of a BBSRC postgraduate studentship. This work was funded by Tenovus Scotland project grant to MD and NM (G13/07) and BBSRC DTG. MD is also supported by the British Heart Foundation (PG/09/048/27675, PG/11/8/28703 and PG/14/43/30889) and Diabetes UK (14/0004853). NM is funded by British Heart Foundation (PG/16/90/32518).

PY - 2017

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N2 - The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.

AB - The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.

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KW - obesity

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DO - 10.1038/s41598-017-10381-3

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Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice

Abstract

Bibliographical note

Keywords

UN SDGs

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Mirela Delibegovic

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