Methionine restriction improves renal insulin signalling in aged kidneys

Louise Grant, Emma K. Lees, Laura A. Forney, Nimesh Mody, Thomas Gettys, Paul A. J. Brown, Heather M. Wilson, Mirela Delibegovic

Research output: Contribution to journalArticle

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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 190 days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer 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.
Original languageEnglish
Pages (from-to)35-43
Number of pages8
JournalMechanisms of Ageing and Development
Volume157
Early online date21 Jul 2016
DOIs
Publication statusPublished - Jul 2016

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Methionine
Insulin
Kidney
Gene Expression
Insulin Resistance
Blood Glucose
S 6
Adiposity
Vacuoles
Histology
Homeostasis
Down-Regulation
Phosphorylation
Diet
Glucose

Keywords

  • methionine
  • diet
  • kidney
  • ageing
  • insulin
  • renoprotection

Cite this

Methionine restriction improves renal insulin signalling in aged kidneys. / Grant, Louise; Lees, Emma K.; Forney, Laura A.; Mody, Nimesh; Gettys, Thomas; Brown, Paul A. J.; Wilson, Heather M.; Delibegovic, Mirela.

In: Mechanisms of Ageing and Development, Vol. 157, 07.2016, p. 35-43.

Research output: Contribution to journalArticle

Grant, Louise ; Lees, Emma K. ; Forney, Laura A. ; Mody, Nimesh ; Gettys, Thomas ; Brown, Paul A. J. ; Wilson, Heather M. ; Delibegovic, Mirela. / Methionine restriction improves renal insulin signalling in aged kidneys. In: Mechanisms of Ageing and Development. 2016 ; Vol. 157. pp. 35-43.
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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 190 days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer 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.",
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