PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

Melanie G. Cree, Bradley R. Newcomer, David N. Herndon, Ting Qian, Dayoung Sun, Beatrice Morio, Jennifer J. Zwetsloot, G. Lynis Dohm, Ricki Y. Fram, Ronald P. Mlcak, Asle Aarsland, Robert R. Wolfe

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background. Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. Methods. A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Results. Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. Conclusion. PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.

Original languageEnglish (US)
Article number9
JournalNutrition and Metabolism
Volume4
DOIs
StatePublished - 2007

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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