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Peroxisomal enhancement of mitochondrial function
Author(s) -
Woodlief Tracey L,
Whitfield Brian R,
Noland Robert C,
Cortright Ronald N
Publication year - 2006
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.20.4.a817-a
Subject(s) - peroxisome , mitochondrion , beta oxidation , biochemistry , palmitic acid , chemistry , fatty acid , biology , receptor
Background A reduction in skeletal muscle (SKM) mitochondrial oxidation of fatty acids is linked to accumulation of bioactive lipids and insulin resistance. In the liver, the cellular defense against lipotoxic accumulation of fatty acids is the peroxisome, which partially oxidizes very long‐ (VLCFA) and long‐chain (LCFA) fatty acids which, as exported acylcarnitines, are utilized by mitochondria more efficiently because entry into the matrix is CPT‐1 independent. To date, little data exists on peroxisomal function in SKM. Purpose To test the direct effects of elevated peroxisomal content on SKM mitochondrial function. Methods Peroxisomes and mitochondria were isolated from rat liver and whole gastrocnemius, respectively. Oxidation rates (as captured 14 CO 2 ) were compared under the following conditions: 1) mitochondria plus 1‐ 14 C Palmitic Acid (LCFA) ± malonyl‐CoA ± increasing peroxisomal content 2) mitochondria plus 1‐ 14 C Lignoceric Acid (VLCFA) ± malonyl‐CoA ± increasing peroxisomal content. Results SKM mitochondrial oxidation of VLCFA was linearly enhanced in the presence of increasing peroxisomal content. Peroxisomal titration did not alter baseline mitochondrial LCFA oxidation, but did rescue a significant portion of LCFA oxidation when malonyl‐CoA was present. Conclusion This study is the first to directly demonstrate that increasing peroxisomal content results in increased SKM mitochondrial oxidation of fatty acids in the inhibited state. These findings suggest a metabolic target for therapeutic intervention that could lower intramuscular lipids suspected to play a major role in the etiology of obesity and diabetes. Support by NIH R15‐DK061314