Clofibrate treatment promotes branched-chain amino acid catabolism and decreases the phosphorylation state of mTOR, eIF4E-BP1, and S6K1 in rat liver

Life Sciences
Hiroki IshiguroYoshiharu Shimomura

Abstract

Leucine stimulates protein synthesis by modulating the mammalian target of rapamycin (mTOR) signaling pathway. We hypothesized that promotion of the branched-chain amino acid (BCAA) catabolism might influence the leucine-induced protein synthesis. Clofibric acid (an active metabolite of clofibrate) is known to promote the BCAA catabolism by activation of branched-chain alpha-keto acid dehydrogenase complex (BCKDC), the rate-limiting enzyme of the BCAA catabolism. In the present study, we examined the phosphorylation state of mTOR, eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and ribosomal protein S6 kinase 1 (S6K1) in liver of rats with or without activation of the BCKDC by clofibrate treatment. Clofibrate-treated rats were prepared by oral administration of clofibrate 5 h before sacrifice. In order to stimulate phosphorylation of components in the mTOR signaling pathway, rats were orally administered with leucine 1 h before sacrifice. Clofibrate treatment almost fully activated hepatic BCKDC and significantly decreased the plasma leucine concentration in rats without leucine administration, resulting in decreased mTOR and 4E-BP1 phosphorylation. Similarly, in rats administered with leucine, clofibrate treatment ...Continue Reading

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Citations

Nov 8, 2006·Journal of Nutritional Science and Vitaminology·Gustavo Bajotto, Yoshiharu Shimomura
Jan 22, 2009·Journal of Nutritional Science and Vitaminology·Yosuke AsaiYoshiharu Shimomura
Jul 16, 2009·Journal of Nutritional Science and Vitaminology·Yoshiharu ShimomuraJuichi Sato
Oct 13, 2009·Toxicology·Malgorzata Knapik-CzajkaJerzy Jaskiewicz
Dec 21, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kyeongjin KimSung Hee Um
May 15, 2013·RNA Biology·Stephanie Maria EsslingerKlaus Förstemann
Nov 1, 2011·JPEN. Journal of Parenteral and Enteral Nutrition·Yoshihiro KadotaYoshiharu Shimomura
May 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dipsikha BiswasThomas Pulinilkunnil
Jan 23, 2020·Nutrients·Yasutomi KameiShinji Miura
Sep 2, 2020·International Journal of Experimental Pathology·Milan Holeček, Melita Vodeničarovová

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