Peroxisome-proliferator-activated receptors (PPARs) α and γ are ligand-dependent transcription factors that are key regulators of lipid and carbohydrate homoeostasis. Fatty acids bind to the ligand-binding domains (LBDs) of PPARα and PPARγ and activate these receptors. To clarify whether fatty-acyl-CoAs interact directly with the LBDs of PPARα and PPARγ, we performed a competition binding assay with radiolabelled KRP-297, a known dual agonist for these receptors. We show here that fatty-acyl-CoAs bind directly to PPARα and PPARγ. Interestingly, fatty-acyl-CoAs, unlike fatty acids, failed to recruit steroid receptor co-activator 1 (SRC-1), on the basis of conformational changes in the LBDs of PPARα and PPARγ. Moreover, fatty-acyl-CoAs also markedly inhibited agonist-induced recruitment of SRC-1. These findings demonstrate that fatty-acyl-CoAs have a novel function in the signalling pathways of PPARα and PPARγ.
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January 2001
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Research Article|
January 08 2001
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to α and γ isoforms of peroxisome-proliferator-activated receptors by competing with agonists
Koji MURAKAMI;
*Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
2To whom correspondence should be addressed (e-mail kouji.murakami@mb2.kyorin-pharm.co.jp).
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Tomohiro IDE;
Tomohiro IDE
1
*Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
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Tomoko NAKAZAWA;
Tomoko NAKAZAWA
*Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
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Takashi OKAZAKI;
Takashi OKAZAKI
*Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
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Toshiro MOCHIZUKI;
Toshiro MOCHIZUKI
*Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1 Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan
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Takashi KADOWAKI
Takashi KADOWAKI
†Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Publisher: Portland Press Ltd
Received:
June 09 2000
Revision Received:
September 26 2000
Accepted:
October 25 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 353 (2): 231–238.
Article history
Received:
June 09 2000
Revision Received:
September 26 2000
Accepted:
October 25 2000
Citation
Koji MURAKAMI, Tomohiro IDE, Tomoko NAKAZAWA, Takashi OKAZAKI, Toshiro MOCHIZUKI, Takashi KADOWAKI; Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to α and γ isoforms of peroxisome-proliferator-activated receptors by competing with agonists. Biochem J 15 January 2001; 353 (2): 231–238. doi: https://doi.org/10.1042/bj3530231
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