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J Biol Chem, Vol. 273, Issue 27, 16710-16714, July 3, 1998
and 
Activators in a Tissue- and Inducer-specific Manner
,
,, and
From the Regulation of gene expression of three putative
long-chain fatty acid transport proteins, fatty acid translocase (FAT),
mitochondrial aspartate aminotransferase (mAspAT), and fatty acid
transport protein (FATP), by drugs that activate peroxisome
proliferator-activated receptor (PPAR) Department of Biochemistry, School
of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274, Japan, the ¶ Laboratoíre de Biologie Moléculaire et
Cellulaire, Universite de Bourgogne, BP138, 21004 Dijon, France,
and the Laboratory of Metabolism, National Institutes of Health,
Bethesda, Maryland 20892
and 
were studied using
normal and obese mice and rat hepatoma cells. FAT mRNA was induced
in liver and intestine of normal mice and in hepatoma cells to various
extents only by PPAR-activating drugs. FATP mRNA was similarly
induced in liver, but to a lesser extent in intestine. The induction
time course in the liver was slower for FAT and FATP mRNA than that
of an mRNA encoding a peroxisomal enzyme. An obligatory role of
PPAR in hepatic FAT and FATP induction was demonstrated, since an
increase in these mRNAs was not observed in PPAR-null mice.
Levels of mAspAT mRNA were higher in liver and intestine of mice
treated with peroxisome proliferators, while levels in hepatoma cells were similar regardless of treatment. In white adipose tissue of KKAy
obese mice, thiazolidinedione PPAR activators (pioglitazone and
troglitazone) induced FAT and FATP more efficiently than the PPAR
activator, clofibrate. This effect was absent in brown adipose tissue.
Under the same conditions, levels of mAspAT mRNA did not change
significantly in these tissues. In conclusion, tissue-specific expression of FAT and FATP genes involves both PPAR and -. Our data suggest that among the three putative long-chain fatty acid transporters, FAT and FATP appear to have physiological roles. Thus,
peroxisome proliferators not only influence the metabolism of
intracellular fatty acids but also cellular uptake, which is likely to
be an important regulatory step in lipid homeostasis.
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