Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84
Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the n...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-01-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.165469 |
| _version_ | 1827768078425915392 |
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| author | Ryuji Ohue-Kitano Hazuki Nonaka Akari Nishida Yuki Masujima Daisuke Takahashi Takako Ikeda Akiharu Uwamizu Miyako Tanaka Motoyuki Kohjima Miki Igarashi Hironori Katoh Tomohiro Tanaka Asuka Inoue Takayoshi Suganami Koji Hase Yoshihiro Ogawa Junken Aoki Ikuo Kimura |
| author_facet | Ryuji Ohue-Kitano Hazuki Nonaka Akari Nishida Yuki Masujima Daisuke Takahashi Takako Ikeda Akiharu Uwamizu Miyako Tanaka Motoyuki Kohjima Miki Igarashi Hironori Katoh Tomohiro Tanaka Asuka Inoue Takayoshi Suganami Koji Hase Yoshihiro Ogawa Junken Aoki Ikuo Kimura |
| author_sort | Ryuji Ohue-Kitano |
| collection | DOAJ |
| description | Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH. |
| first_indexed | 2024-03-11T12:07:10Z |
| format | Article |
| id | doaj.art-ecafa7ca37954e389e6d0e6f51ad1a89 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:10Z |
| publishDate | 2023-01-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-ecafa7ca37954e389e6d0e6f51ad1a892023-11-07T16:25:07ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-01-0182Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84Ryuji Ohue-KitanoHazuki NonakaAkari NishidaYuki MasujimaDaisuke TakahashiTakako IkedaAkiharu UwamizuMiyako TanakaMotoyuki KohjimaMiki IgarashiHironori KatohTomohiro TanakaAsuka InoueTakayoshi SuganamiKoji HaseYoshihiro OgawaJunken AokiIkuo KimuraMedium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH.https://doi.org/10.1172/jci.insight.165469HepatologyInflammation |
| spellingShingle | Ryuji Ohue-Kitano Hazuki Nonaka Akari Nishida Yuki Masujima Daisuke Takahashi Takako Ikeda Akiharu Uwamizu Miyako Tanaka Motoyuki Kohjima Miki Igarashi Hironori Katoh Tomohiro Tanaka Asuka Inoue Takayoshi Suganami Koji Hase Yoshihiro Ogawa Junken Aoki Ikuo Kimura Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 JCI Insight Hepatology Inflammation |
| title | Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 |
| title_full | Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 |
| title_fullStr | Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 |
| title_full_unstemmed | Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 |
| title_short | Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84 |
| title_sort | medium chain fatty acids suppress lipotoxicity induced hepatic fibrosis via the immunomodulating receptor gpr84 |
| topic | Hepatology Inflammation |
| url | https://doi.org/10.1172/jci.insight.165469 |
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