Rifampicin-Induced Hepatic Lipid Accumulation: Association with Up-Regulation of Peroxisome Proliferator-Activated Receptor [gamma] in Mouse Liver

Previous study found that rifampicin caused intrahepatic cholestasis. This study investigated the effects of rifampicin on hepatic lipid metabolism. Mice were orally administered with rifampicin (200 mg/kg) daily for different periods. Results showed that serum TG level was progressively reduced aft...

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Bibliographic Details
Published in:PloS one 2016-11, Vol.11 (11), p.e0165787
Main Authors: Huang, Jia-Hui, Zhang, Cheng, Zhang, Da-Gang, Li, Lu, Chen, Xi, Xu, De-Xiang
Format: Article
Language:English
Subjects:
DNA binding proteins
Fatty acid synthesis
Fatty acids
Liver
Liver diseases
Physiological aspects
Rifampin
RNA
Transcription (Genetics)
Type 2 diabetes
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Summary:Previous study found that rifampicin caused intrahepatic cholestasis. This study investigated the effects of rifampicin on hepatic lipid metabolism. Mice were orally administered with rifampicin (200 mg/kg) daily for different periods. Results showed that serum TG level was progressively reduced after a short elevation. By contrast, hepatic TG content was markedly increased in rifampicin-treated mice. An obvious hepatic lipid accumulation, as determined by Oil Red O staining, was observed in mice treated with rifampicin for more than one week. Moreover, mRNA levels of Fas, Acc and Scd-1, several key genes for fatty acid synthesis, were elevated in rifampicin-treated mice. In addition, the class B scavenger receptor CD36 was progressively up-regulated by rifampicin. Interestingly, hepatic SREBP-1c and LXR-[alpha], two important transcription factors that regulate genes for hepatic fatty acid synthesis, were not activated by rifampicin. Instead, hepatic PXR was rapidly activated in rifampicin-treated mice. Hepatic PPAR[gamma], a downstream target of PXR, was transcriptionally up-regulated. Taken together, the increased hepatic lipid synthesis and uptake of fatty acids from circulation into liver jointly contribute to rifampicin-induced hepatic lipid accumulation. The increased uptake of fatty acids from circulation into liver might be partially attributed to rifampicin-induced up-regulation of PPAR[gamma] and its target genes.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0165787