Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 25, Pages 10709-10713Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0704024104
Keywords
peroxisome proliferator-activated receptor (PPAR)delta; high-fat diet; fatty acid oxidation
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Funding
- Intramural NIH HHS [Z01 AG000425] Funding Source: Medline
- NIA NIH HHS [R01 AG000425, R37 AG000425, R56 AG000425] Funding Source: Medline
- NIDDK NIH HHS [F32 DK076410, P30 DK056341-06, P30 DK056341, P30 DK056341-07, 1F32DK076410, R01 DK074700, K01 DK063051, P60 DK20579-28, P60 DK020579] Funding Source: Medline
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A number of studies have reported that a high-fat diet induces increases in mitochondrial fatty acid oxidation enzymes in muscle. In contrast, in two recent studies raising plasma free fatty acids (FFA) resulted in a decrease in mitochondria. In this work, we reevaluated the effects of raising FFA on muscle mitochondrial biogenesis and capacity for fat oxidation. Rats were fed a high-fat diet and given daily injections of heparin to raise FFA. This treatment induced an increase in mitochondrial biogenesis in muscle, as evidenced by increases in mitochondrial enzymes of the fatty acid oxidation pathway, citrate cycle, and respiratory chain, with an increase in the capacity to oxidize fat, as well as an increase in mitochondrial DNA copy number. Raising FFA also resulted in an increase in binding of peroxisome proliferator-activated receptor (PPAR) delta to the PPAR response element on the carnitine palmitoyltransferase 1 promoter. We interpret our results as evidence that raising FFA induces an increase in mitochondrial biogenesis in muscle by activating PPAR delta.
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