[1]代棠瑜 钱海燕 王蕾.G蛋白偶联受体120在心血管疾病中的机制及转化研究进展[J].心血管病学进展,2026,(2):159.[doi:10.16806/j.cnki.issn.1004-3934.2026.02.013]
　DAI Tangyu,QIAN Haiyan,WANG Lei.Mechanisms and Translational Research of G protein-coupled receptor 120 in Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2026,(2):159.[doi:10.16806/j.cnki.issn.1004-3934.2026.02.013]
点击复制

G蛋白偶联受体120在心血管疾病中的机制及转化研究进展()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2026年2期
页码:
159
栏目:
综述
出版日期:
2026-02-25

文章信息/Info

Title:
Mechanisms and Translational Research of G protein-coupled receptor 120 in Cardiovascular Disease
作者:
代棠瑜1 钱海燕 2 王蕾 3
(1.首都医科大学基础医学院,北京 100069;2.首都医科大学附属北京安贞医院心内冠心病中心二区,北京 100029;3.首都医科大学公共卫生学院营养和食品卫生系 心血管重塑相关疾病教育部重点实验室 环境与衰老北京市重点实验室,北京 100069)
Author(s):
DAI Tangyu1; QIAN Haiyan2; WANG Lei3
?1.School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China; 2.Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China; 3.Department of Nutrition and Food Hygiene,School of Public Health,Capital Medical University,Key Laboratory of Cardiovascular Remodeling-Related Diseases,Ministry of Education,Beijing Key Laboratory of Environmental and Aging,Beijing 100069.China)
关键词:
G蛋白偶联受体120; 游离脂肪酸受体4; G蛋白偶联受体信号转导; 心血管疾病; 病理生理学机制; 转化应用
Keywords:
G protein-coupled receptor 120;  Free fatty acid receptor 4;  G protein-coupled receptor signal transduction;  Cardiovascular disease;  Pathophysiological mechanism;  Translational application
DOI:
10.16806/j.cnki.issn.1004-3934.2026.02.013
摘要:
G蛋白偶联受体120作为长链脂肪酸（尤其是ω-3多不饱和脂肪酸）的关键膜受体，通过整合代谢、炎症及细胞稳态调控网络，在心血管疾病中发挥多维度保护作用。本文系统综述了G蛋白偶联受体120的分子特征、组织分布及其双重信号转导机制（G蛋白依赖与β-arrestin依赖通路），重点阐述其在心血管疾病中的病理生理学机制及转化研究进展，并探讨其作为心血管疾病新兴治疗靶标的潜在应用价值及挑战。
Abstract:
The G protein-coupled receptor 120,a key membrane receptor for long-chain fatty acids (particularly ω-3 polyunsaturated fatty acids),exerts multifaceted protective roles in cardiovascular diseases by coordinating metabolic,inflammatory,and cellular homeostatic regulatory networks. This article systematically reviews the molecular characteristics,tissue distribution,and dual signaling transduction mechanisms(G protein-dependent and β-arrestin-dependent pathways) of G protein-coupled receptor 120,focusing on elucidating its mechanisms in cardiovascular pathologies and advances in translational research. Additionally,it explores the potential applications and challenges of G protein-coupled receptor 120 as an emerging therapeutic target for cardiovascular diseases

参考文献/References:

[1] Lymperopoulos A,Suster M S,Borges J I. Short-chain fatty acid receptors and cardiovascular function[J].Int J Mol Sci,2022,23(6):3303.

[2] Zhang S,Roth BL. Sensing unsaturated fatty acids:Insights from GPR120 signaling[J].Cell Res,2023,33(9):657-658.

[3] Carullo G,Mazzotta S,Vega-Holm M,et al. GPR120/FFAR4 pharmacology:focus on agonists in type 2 diabetes mellitus drug discovery[J]. J Med Chem,2021,64(8):4312-4332.

[4] Mao C,Xiao P,Tao XN,et al. Unsaturated bond recognition leads to biased signal in a fatty acid receptor[J]. Science,2023,380(6640):eadd6220.

[5] O’Connell TD,Murphy KA,Zhang N,et al. Signaling through free fatty acid receptor 4 attenuates cardiometabolic disease[J]. Physiology(Bethesda,),2022,37(6):311-322.

[6] Zhang X,Guseinov AA,Jenkins L,et al. Structural basis for the ligand recognition and signaling of free fatty acid receptors[J]. Sci Adv,2024,10(2):eadj2384.

[7] Samovski D,Jacome-Sosa M,Abumrad NA. Fatty acid transport and signaling:Mechanisms and physiological implications[J]. Annu Rev Physiol,2023,85:317-337.

[8] Nakajima S,Demers G,Machuca-Parra AI,et al. Central activation of the fatty acid sensor GPR120 suppresses microglia reactivity and alleviates sickness- and anxiety-like behaviors[J]. J Neuroinflammation,2023,20(1):302.

[9] Yasumatsu K,Iwata S,Inoue M,et al. Fatty acid taste quality information via GPR120 in the anterior tongue of mice[J]. Acta Physiol (Oxf),2019,226(1):e13215.

[10] Schilperoort M,van Dam AD,Hoeke G,et al. The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat[J]. EMBO Mol Med,2018,10(3):e8047.

[11] Yasuda T,Harada N,Hatoko T,et al. Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding[J]. Am J Physiol Endocrinol Metab,2023,324(5):E449-E460.

[12] Sithole C,Pieterse C,Howard K,et al. GPR120 inhibits RANKL-induced osteoclast formation and resorption by attenuating reactive oxygen species production in RAW264.7 murine macrophages[J]. Int J Mol Sci,2021,22(19):10544.

[13] Yu H,Yang W,Huang J,et al. GPR120 induces regulatory dendritic cells by inhibiting HK2-dependent glycolysis to alleviate fulminant hepatic failure[J]. Cell Death Dis,2021,13(1):1.

[14] Kimura I,Ichimura A,Ohue-Kitano R,et al. Free fatty acid receptors in health and disease[J]. Physiol Rev,2020,100(1):171-210.

[15] Xu Z,Shao Z. Dynamic mechanism of GPCR-mediated β-arrestin:a potential therapeutic agent discovery of biased drug[J]. Signal Transduct Target Ther,2022,7(1):283.

[16] Jia X,Liu W. Vaccarin improves insulin sensitivity and glucose uptake in diet-induced obese mice via activation of GPR120-PI3K/AKT/GLUT4 pathway[J]. Biochem Biophys Res Commun,2022,634:189-195.

[17] Szukiewicz D. Potential therapeutic exploitation of G protein-coupled receptor 120 (GPR120/FFAR4) signaling in obesity-related metabolic disorders[J]. Int J Mol Sci,2025,26(6):2501.

[18] Hilgendorf KI,Johnson CT,Mezger A,et al. Omega-3 fatty acids activate ciliary FFAR4 to control adipogenesis[J]. Cell,2019,179(6):1289-1305.e21.

[19] Duah M,Zhang K,Liang Y,et al. Immune regulation of poly unsaturated fatty acids and free fatty acid receptor 4[J]. J Nutr Biochem,2023,112:109222.

[20] Yan CH,Liu HW,Tian XX,et al. AMPKα2 controls the anti-atherosclerotic effects of fish oils by modulating the SUMOylation of GPR120[J]. Nat Commun,2022,13(1):7721.

[21] Kiepura A,Stachyra K,Olszanecki R. Anti-atherosclerotic potential of free fatty acid receptor 4 (FFAR4)[J]. Biomedicines,2021,9(5):467.

[22] Kiepura A,Stachyra K,Wi?niewska A,et al. The anti-atherosclerotic action of FFAR4 agonist TUG-891 in ApoE-knockout mice is associated with increased macrophage polarization towards M2 phenotype[J]. Int J Mol Sci,2021,22(18):9772.

[23] An T,Zhang X,Li H,et al. GPR120 facilitates cholesterol efflux in macrophages through activation of AMPK signaling pathway[J]. FEBS J,2020,287(23):5080-5095.

[24] Liu R,Cheng F,Zeng K,et al. GPR120 agonist GW9508 ameliorated cellular senescence induced by ox-LDL[J]. ACS Omega,2020,5(50):32195-32202.

[25] Li J,Tian Z,Zhang T,et al. Single-cell view and a novel protective macrophage subset in perivascular adipose tissue in T2DM[J]. Cell Mol Biol Lett,2024,29(1):148.

[26] Sung PH,Yeh JN,Yin TC,et al. Extracorporeal shockwave therapy rescued mouse critical limb ischemia via upregulating GPR120 against inflammation and promoting angiogenesis for restoring the blood flow in ischemic zone-experimental study[J]. Int J Surg,2025,111(3):2414-2429.

[27] Zhao C,Zhou J,Meng Y,et al. DHA sensor GPR120 in host defense exhibits the dual characteristics of regulating dendritic cell function and skewing the balance of Th17/tregs[J]. Int J Biol Sci,2020,16(3):374-387.

[28] Lazzarin T,Martins D,Ballarin RS,et al. The role of omega-3 in attenuating cardiac remodeling and heart failure through the oxidative stress and inflammation pathways[J]. Antioxidants (Basel),2023,12(12):2067.

[29] O’Connell TD,Block R C,Huang SP,et al. ω3-polyunsaturated fatty acids for heart failure:Effects of dose on efficacy and novel signaling through free fatty acid receptor 4[J]. J Mol Cell Cardiol,2017,103:74-92.

[30] Murphy KA,Harsch BA,Healy CL,et al. Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload[J]. Cardiovasc Res,2022,118(4):1061-1073.

[31] Wang CP,Lee CC,Wu DY,et al. Differential effects of EPA and DHA on PPARγ-mediated sympathetic innervation in infarcted rat hearts by GPR120-dependent and -independent mechanisms[J]. J Nutr Biochem,2022,103:108950.

[32] Chen WT,Chen SY,Wu DW,et al. Effect of icosapent ethyl on susceptibility to ventricular arrhythmias in postinfarcted rat hearts:Role of GPR120-mediated connexin43 phosphorylation[J]. J Cell Mol Med,2020,24(16):9267-9279.

[33] Yang X,Li X,Hu M,et al. EPA and DHA differentially improve insulin resistance by reducing adipose tissue inflammation-targeting GPR120/PPARγ pathway[J]. J Nutr Biochem,2024,130:109648.

[34] Du YQ,Sha XY,Cheng J,et al. Endogenous lipid-GPR120 signaling modulates pancreatic islet homeostasis to different extents[J]. Diabetes,2022,71(7):1454-1471.

[35] Jin C,Chen H,Xie L,et al. GPCRs involved in metabolic diseases:pharmacotherapeutic development updates[J]. Acta Pharmacol Sin,2024,45(7):1321-1336.

[36] Ghislain J,Poitout V. Targeting lipid GPCRs to treat type?2 diabetes mellitus - progress and challenges[J]. Nat Rev Endocrinol,2021,17(3):162-175.

[37] McCloskey AG,Miskelly MG,Flatt PR,et al. Pharmacological potential of novel agonists for FFAR4 on islet and enteroendocrine cell function and glucose homeostasis[J]. Eur J Pharm Sci,2020,142:105104.

[38] Yang L,Lei XT,Huang Q,et al. A novel GPR120-selective agonist promotes insulin secretion and improves chronic inflammation[J]. Life Sci,2021,269:119029.

[39] Davenport AP,Scully CCG,de Graaf C,et al. Advances in therapeutic peptides targeting G protein-coupled receptors[J]. Nat Rev Drug Discov,2020,19(6):389-413.

[40] Pedroni L,Perugino F,Magnaghi F,et al. Free fatty acid receptors beyond fatty acids:A computational journey to explore peptides as possible binders of GPR120[J]. Curr Res Food Sci,2024,8:100710.

更新日期/Last Update: 2026-05-28