Chronic, in vivo, PPARalpha activation prevents lipid overload in rat liver induced by high fat feeding.
OBJECTIVE
Peroxisome proliferator-activated receptors (PPAR's) are lipid sensors and when activated they modify gene expression of proteins regulating fatty acid (FA) metabolism in liver cells. The aim of the present study was to examine the in vivo effects of PPAR alpha and gamma activation combined with high fat diet (HFD) feeding on the lipid content and FA profile in the liver.


METHODS
We assessed whether in vivo activation of PPARs (alpha or gamma) affects lipid accumulation in the liver induced by HFD feeding. Furthermore, as PPAR activity may be a key factor regulating long chain fatty acids (LCFA) flux and subsequent LCFA utilization in the liver, we prompted to investigate also the FA profile in different lipid fractions in this tissue.


RESULTS
PPARalpha agonist (WY 14,643) treatment reduced the accumulation of liver lipids free fatty acids (FFA:-30%, diacylglycerols DAG: -27% and triacylglycerols TAG: -60%, p<0.05) evoked by HFD feeding. Interestingly, with PPARgamma stimulation liver lipid content was further elevated comparing to the effects of HFD (phospholipids PL: +48%, DAG: +231%, TAG: +346%, p<0.05).


CONCLUSIONS
These findings suggest that in vivo PPARalpha and PPARgamma activation combined with HFD feeding exert different effects on lipid content in rat's liver and in vivo PPARalpha activation may prevent lipid overload in the liver cells provoked by HFD feeding.
Wierzbicki
M
M
Department of Physiology, Medical University of Bialystok, Bialystok, Poland. adrian@amb.edu.pl
Chabowski
A
A
Zendzian-Piotrowska
M
M
Harasim
E
E
Górski
J
J
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood; D005234:Fatty Liver / Q000517:prevention & control*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D011743:Pyrimidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology
D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; D045162:Thiazolidinediones; C006253:pirinixic acid; D000077205:Pioglitazone