PPAR-alpha 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

Overview

Journal Nutr Metab (Lond)

Publisher Biomed Central

Date 2007 Apr 25

PMID 17451602

Citations 29

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat beta-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-alpha 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-alpha agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-alpha 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-theta activation during hyper-insulinemia decreased significantly following PPAR-alpha treatment.

Conclusion: PPAR-alpha 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.

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