Proceedings for Annual Meeting of The Japanese Pharmacological Society
Online ISSN : 2435-4953
The 92nd Annual Meeting of the Japanese Pharmacological Society
Session ID : 92_1-O-13
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PPARα agonist-induced nicotinic receptor α2 subunit gene expression in the rat liver
*Tetsuro UrushidaniYoko AmagaseYumiko Mizukawa
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Abstract

In our previous study, we extracted many genes commonly up-regulated by PPARα agonists (fibrates) in the rat liver using the transcriptome database created by The Toxicogenomics Project (TG-GATEs). Of these, nicotinic receptor α2 subunit (Chrna2) and acetylcholine (Ach) esterase anchoring protein (Colq) were markedly up-regulated by fibrates without any changes in other Ach receptors. Their induction was confirmed by quantitative PCR in the rats received fenofibrate for 3 days. The expression of Chrna2 was largely increased with repeated administration but not observed in the primary cultured hepatocytes. In the meantime, it was reported that Chrna2 was up-regulated in PPARγ-activated beige adipocytes and Ach released from immune cells stimulated the receptor to induce thermogenic protein, UCP1(Nature Med. 24 814, 2018).  We then checked UCPs and found that UCP3, not UCP1, was markedly up-regulated by fibrates. The present data suggest that hepatocytes have a specific energy consuming system, PPARα>Chrna2>UCP3, similar to but different from that in adipocytes.

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