Differential effects of in vivo PPAR alpha and gamma activation on fatty acid transport proteins expression and lipid content in rat liver.
Peroxisome proliferator-activated receptors (PPAR;s) serve as lipid sensors and when activated modify gene expression of proteins highly involved in the regulation of fatty acid metabolism. Recently, the accumulation of lipids in liver was shown to be depended on the excessive protein-mediated transmembrane transport of long chain fatty acids (LCFAs). The aim of the present study was to determine the in vivo effects of PPARalpha and gamma activation at two levels: 1) on the expression of fatty acid transporters, 2) on the content and fatty acids saturation status of lipids in rats liver. PPARalpha agonist (WY 14,643) treatment upregulated the liver expression of FAT/CD36 (+20%, p<0.05) and did not significantly affect the content of FABPpm and FATP-1. Accordingly there was a significant increase in the content of phospholipid (+12%, p<0.05), diacylglycerol (+65%, p<0.05) and triacylglycerol (+46%, p<0.05) fractions followed PPARalpha activation. In contrast, pioglitazone (PPARgamma agonist) had no effect on the content of fatty acid transporters (FAT/CD36, FABPpm and FATP-1) as well as the content of liver lipid fractions with the exception for triacylglycerols, which have been reduced significantly (-89%, p<0.05). These findings suggest that in vivo PPARalpha and PPARgamma activation exert different effects on both the expression of fatty acid transporters and lipid content in rat's liver.
Department of Physiology, Medical University of Bialystok, Mickiewicza 2C street, Bialystok, Poland.
M
M
Wierzbicki
A
A
Chabowski
M
M
Zendzian-Piotrowska
J
J
Gorski
D000818:Animals; D050612:Fatty Acid Transport Proteins / Q000187:drug effects / Q000235:genetics; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D000077205:Pioglitazone; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology
D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D047493:PPAR alpha; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D045162:Thiazolidinediones; C006253:pirinixic acid; D000077205:Pioglitazone