Methionine restriction improves renal insulin signalling in aged kidneys.

Grant, Louise and Lees, Emma K and Forney, Laura A and Mody, Nimesh and Gettys, Thomas and Brown, Paul A J and Wilson, Heather M and Delibegovic, Mirela (2016) Methionine restriction improves renal insulin signalling in aged kidneys. Mechanisms of Ageing and Development, 157. pp. 35-43. ISSN 1872-6216

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Abstract

Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein UCP1 was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, FGF21, klotho, and β-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.

Item Type:	Article
Additional Information and Comments:	NOTICE: this is the author’s version of a work that was accepted for publication in Mechanisms of Ageing and Development. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mechanisms of Ageing and Development, Vol 157, July 2016. Available at http://www.sciencedirect.com/science/article/pii/S0047637416301038
Faculty / Department:	Faculty of Human and Digital Sciences > School of Health and Sport Sciences
Depositing User:	Emma Lees
Date Deposited:	12 Jun 2017 15:02
Last Modified:	12 Jun 2017 15:02
URI:	https://hira.hope.ac.uk/id/eprint/1609

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