The lactate receptor GPR81 mediates hepatic lipid metabolism and the therapeutic effect of metformin on experimental NAFLDs
Copyright © 2022 Elsevier B.V. All rights reserved..
The lactate receptor G protein-coupled receptor 81 (GPR81) has been recently implicated in lipolysis in adipose tissue. In this study, we accidently discovered the role of GPR81 in hepatic lipid metabolism. Data clearly showed that hepatic GPR81 was markedly up-regulated in fasted mice, whereas it was severely down-regulated in obese mice. Genetic deficiency of GPR81 impaired ketogenic response, enhanced hepatic lipid accumulation, and exacerbated hepatosteatosis under acute fasting conditions. Mechanically, we demonstrated that hepatic GPR81 might function as a modulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), activate the downsream transcription of liver carnitine o-palmitoyltransferase 1(L-CPT1), and thereby control the influx of fatty acids into mitochondria for β-oxidation. Importantly, metformin improved experimental nonalcoholic fatty liver disease (NAFLDs) in a GPR81-dependent manner. Collectively, GPR81 was critical for hepatic lipid homeostasis and activation of hepatic GPR81 might represent a promising strategy for the treatment of obesity and its associated metabolic disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:924 |
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| Enthalten in: |
European journal of pharmacology - 924(2022) vom: 05. Juni, Seite 174959 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Guanglu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.05.2022 Date Revised 12.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2022.174959 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The lactate receptor GPR81 mediates hepatic lipid metabolism and the therapeutic effect of metformin on experimental NAFLDs |
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| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a The lactate receptor G protein-coupled receptor 81 (GPR81) has been recently implicated in lipolysis in adipose tissue. In this study, we accidently discovered the role of GPR81 in hepatic lipid metabolism. Data clearly showed that hepatic GPR81 was markedly up-regulated in fasted mice, whereas it was severely down-regulated in obese mice. Genetic deficiency of GPR81 impaired ketogenic response, enhanced hepatic lipid accumulation, and exacerbated hepatosteatosis under acute fasting conditions. Mechanically, we demonstrated that hepatic GPR81 might function as a modulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), activate the downsream transcription of liver carnitine o-palmitoyltransferase 1(L-CPT1), and thereby control the influx of fatty acids into mitochondria for β-oxidation. Importantly, metformin improved experimental nonalcoholic fatty liver disease (NAFLDs) in a GPR81-dependent manner. Collectively, GPR81 was critical for hepatic lipid homeostasis and activation of hepatic GPR81 might represent a promising strategy for the treatment of obesity and its associated metabolic disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GPR81 | |
| 650 | 4 | |a Hepatic lipid metabolism | |
| 650 | 4 | |a Metformin | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a PGC-1α | |
| 650 | 7 | |a Fatty Acids |2 NLM | |
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| 700 | 1 | |a Dai, Yufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Yongheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Haitao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Wei |e verfasserin |4 aut | |
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