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PPAR‐α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children
Author(s) -
Cree Melanie G,
Newcomer Bradley R,
Herndon David N,
Qian Ting,
Sun Dayoung,
Morio Beatrice,
Zwetsloot Jennifer J,
Dohm G. Lynis,
Fram Ricki Y,
Aarsland Asle,
Wolfe Robert R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a839
Subject(s) - zoology , medicine , biology
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 trauma induced insulin resistance. 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 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. 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 and carnitine and liver triglycerides did not change with either treatment. PKC‐ activation during hyper‐insulinemia decreased significantly following PPAR‐α treatment. Impaired palmitate oxidation and increased PKC activity are related to reduced insulin sensitivity in acute trauma, but a relation between these two responses cannot be attributed to alterations in intracellular lipid concentrations.