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游离脂肪酸受体作为肝脏疾病的介质和治疗靶点

Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease.

作者信息

Secor Jordan D, Fligor Scott C, Tsikis Savas T, Yu Lumeng J, Puder Mark

机构信息

Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.

出版信息

Front Physiol. 2021 Apr 7;12:656441. doi: 10.3389/fphys.2021.656441. eCollection 2021.

DOI:10.3389/fphys.2021.656441
PMID:33897464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8058363/
Abstract

Free fatty acid receptors (FFARs) are a class of G protein-coupled receptors (GPCRs) that have wide-ranging effects on human physiology. The four well-characterized FFARs are FFAR1/GPR40, FFAR2/GPR43, FFAR3/GPR41, and FFAR4/GPR120. Short-chain (<6 carbon) fatty acids target FFAR2/GPR43 and FFAR3/GPR41. Medium- and long-chain fatty acids (6-12 and 13-21 carbon, respectively) target both FFAR1/GPR40 and FFAR4/GPR120. Signaling through FFARs has been implicated in non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), intestinal failure-associated liver disease (IFALD), and a variety of other liver disorders. FFARs are now regarded as targets for therapeutic intervention for liver disease, diabetes, obesity, hyperlipidemia, and metabolic syndrome. In this review, we provide an in-depth, focused summary of the role FFARs play in liver health and disease.

摘要

游离脂肪酸受体（FFARs）是一类对人体生理有广泛影响的G蛋白偶联受体（GPCRs）。四种已被充分表征的FFARs分别是FFAR1/GPR40、FFAR2/GPR43、FFAR3/GPR41和FFAR4/GPR120。短链（<6个碳原子）脂肪酸作用于FFAR2/GPR43和FFAR3/GPR41。中链和长链脂肪酸（分别为6 - 12个和13 - 21个碳原子）则作用于FFAR1/GPR40和FFAR4/GPR120。通过FFARs的信号传导与非酒精性脂肪性肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、肠衰竭相关肝病（IFALD）以及多种其他肝脏疾病有关。FFARs现在被视为肝病、糖尿病、肥胖、高脂血症和代谢综合征治疗干预的靶点。在本综述中，我们对FFARs在肝脏健康和疾病中所起的作用进行了深入、重点突出的总结。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08d/8058363/0557ce63fe33/fphys-12-656441-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08d/8058363/878f11615416/fphys-12-656441-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08d/8058363/0557ce63fe33/fphys-12-656441-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08d/8058363/878f11615416/fphys-12-656441-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08d/8058363/0557ce63fe33/fphys-12-656441-g002.jpg

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Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease.

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本文引用的文献

[1]
GPR40 deficiency is associated with hepatic FAT/CD36 upregulation, steatosis, inflammation, and cell injury in C57BL/6 mice.

Am J Physiol Endocrinol Metab. 2021-1-1

[2]
Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

J Pediatr. 2021-3

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Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals.

Gut. 2021-5

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Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease.

Sci Rep. 2020-7-29

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Biomedicines. 2020-6-8

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G-Protein-Coupled Receptors 120 Agonist III Improves Hepatic Inflammation and ER Stress in Steatohepatitis.

Dig Dis Sci. 2021-4

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The rs11187533 C>T Variant of the FFAR4 Gene Is Associated with Lower Levels of Fasting Glucose and Decreases in Markers of Liver Injury in Children with Obesity.

Ann Nutr Metab. 2020

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Sci Rep. 2019-11-12

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Free Fatty Acid Receptors in Health and Disease.

Physiol Rev. 2019-9-5

[10]
Involvement of G-Protein-Coupled Receptor 40 in the Inhibitory Effects of Docosahexaenoic Acid on SREBP1-Mediated Lipogenic Enzyme Expression in Primary Hepatocytes.

Int J Mol Sci. 2019-5-28

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