[Effect of Endotoxin on the expression of peroxisome proliferator-activated receptor alpha in the development of nonalcoholic steatohepatitis in rats].
OBJECTIVE
To study the effect of endotoxin on the expression of peroxisome proliferator-activated receptor alpha (PPARa) in the development of nonalcoholic steatohepatitis in rats.


METHODS
A model of nonalcoholic steatohepatitis (NASH) was developed with Wistar rats fed a chow containing 20% maize oil for 14 weeks. The endotoxin group rats were intraperitoneally injected with lipopolysaccharide (LPS, 1 g/L, 3.0 ml/kg) once 4 hours before the end of the experiment. The concentrations of lipids, endotoxin, tumor necrosis factor-a, malondialdehyde, free fatty acid in plasma and hepatic tissues were determined and the degree of hepatocytic steatosis was studied. The expression of PPARa mRNA in hepatic tissues was measured using reverse transcriptase-polymerase chain reaction (RT-PCR).


RESULTS
The expression of PPARa mRNA in the hepatic tissue of the LPS group was downregulated markedly in comparison to that of the control group. The level of free fatty acid and endotoxin by secreting tumor necrosis factor-a increased and triglyceride accumulated in the liver caused malondialdehyde content to increase, then lipid peroxidation process enhanced and ALT activity increased. Thus, hepatic injury and inflammatory reaction could be accelerated.


CONCLUSIONS
Endotoxemia can enhance hepatocellular steatosis and lead to NASH due to its downregulating the expression of PPARa mRNA.
Li
Xia
X
Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, China.
Han
De Wu
DW
Zhao
Long Feng
LF
Yin
Lei
L
D000818:Animals; D015536:Down-Regulation; D004731:Endotoxins / Q000494:pharmacology*; D005234:Fatty Liver / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004731:Endotoxins; D047493:PPAR alpha; D012333:RNA, Messenger