Abstract
Fenofibrate and fasting are known to regulate several genes involved in lipid metabolism in a similar way. In this study measuring several mitochondrial enzyme activities, we demonstrate that, in contrast to citrate synthase and complex II, cytochrome c oxidase (COX) is a specific target of these two treatments. In mouse liver organelles, Western blot experiments indicated that mitochondrial levels of p43, a mitochondrial T3 receptor, and mitochondrial peroxisome proliferator activated receptor (mt-PPAR), previously described as a dimeric partner of p43 in the organelle, are increased by both fenofibrate and fasting. In addition, in PPAR alpha-deficient mice, this influence was abolished for mt-PPAR but not for p43, whereas the increase in COX activity was not altered. These data indicate that: (1) PPAR alpha is involved in specific regulation of mt-PPAR expression by both treatments; (2) fenofibrate and fasting regulate the mitochondrial levels of p43 and thus affect the efficiency of the direct T3 mitochondrial pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Citrate (si)-Synthase / metabolism
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Crosses, Genetic
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DNA-Binding Proteins / metabolism
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Dimerization
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Electron Transport Complex II
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Electron Transport Complex IV / metabolism
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Fasting
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Fenofibrate / pharmacology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / enzymology
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Mitochondria, Liver / physiology*
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Multienzyme Complexes / metabolism
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Organelles / drug effects
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Organelles / physiology
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Oxidoreductases / metabolism
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Receptors, Cytoplasmic and Nuclear / deficiency
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology*
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Succinate Dehydrogenase / metabolism
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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DNA-Binding Proteins
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Multienzyme Complexes
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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Oxidoreductases
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Electron Transport Complex II
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Succinate Dehydrogenase
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Electron Transport Complex IV
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Citrate (si)-Synthase
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Fenofibrate