Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease

Rocco Barazzoni, Xinxia Zhu, Mark Deboer, Rakesh Datta, Michael D. Culler, Michela Zanetti, Gianfranco Guarnieri, Daniel L. Marks

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Skeletal muscle mitochondrial dysfunction and insulin resistance occur in chronic kidney disease. Ghrelin is a gastric hormone previously shown to enhance muscle mitochondrial enzyme activities and AKT-mediated insulin signaling independent of food intake in healthy rats. Here we determined the impact of ghrelin treatment on anorexia, skeletal muscle mitochondrial oxidative capacity, AKT phosphorylation as a measure of insulin signaling, and lean body mass in a rat model of chronic kidney disease. Ghrelin infusion promoted higher food intake and lean body mass. Further, although muscle mitochondrial enzyme activities were low in the rats with CKD (chronic kidney disease), they normalized with ghrelin treatment, a change that was consistent with the increase in the transcript levels of regulators of mitochondrial biogenesis and lipid metabolism. This was associated with a lower muscle triglyceride content and higher AKT phosphorylation. Pair-feeding showed that mitochondrial effects of ghrelin are independent of changes in food intake, whereas combined ghrelin treatment and higher food intake were needed to enhance AKT phosphorylation. Thus, ghrelin-induced muscle mitochondrial changes and lower tissue triglycerides could favor insulin action and muscle anabolism in the presence of improvement in food intake. Our study shows that combined effects of ghrelin on appetite and muscle mitochondria improve muscle metabolic and nutritional alterations in chronic kidney disease. This could have potential beneficial impact on patient morbidity and survival.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalKidney International
Volume77
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Insulin resistance
  • Mitochondria
  • Nutrition

ASJC Scopus subject areas

  • Nephrology

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