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1.山东第一医科大学第一附属医院(山东省千佛山医院)药学部/山东省儿童药物临床评价与研发工程技术研究中心/山东省医药卫生临床药学重点实验室,济南 250014
2.山东中医药大学药学院,济南 250355
硕士研究生。研究方向:临床药学。E-mail:zhu6919@ 163.com
主任药师,硕士生导师。研究方向:临床药学。 E-mail:li_xyan@126.com
收稿:2025-05-08,
修回:2025-09-22,
录用:2025-09-24,
纸质出版:2025-10-30
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朱艳娇,高蕊,宗慧颖,等.GLP-1受体激动剂降脂作用机制及临床应用的研究进展 [J].中国药房,2025,36(20):2615-2620.
ZHU Yanjiao,GAO Rui,ZONG Huiying,et al.Research progress on the lipid-lowering mechanisms and clinical application of GLP-1 receptor agonists[J].ZHONGGUO YAOFANG,2025,36(20):2615-2620.
朱艳娇,高蕊,宗慧颖,等.GLP-1受体激动剂降脂作用机制及临床应用的研究进展 [J].中国药房,2025,36(20):2615-2620. DOI: 10.6039/j.issn.1001-0408.2025.20.23.
ZHU Yanjiao,GAO Rui,ZONG Huiying,et al.Research progress on the lipid-lowering mechanisms and clinical application of GLP-1 receptor agonists[J].ZHONGGUO YAOFANG,2025,36(20):2615-2620. DOI: 10.6039/j.issn.1001-0408.2025.20.23.
胰高血糖素样肽1(GLP-1)受体激动剂是一类新型降糖药物,兼具降脂和心血管保护作用,利拉鲁肽和司美格鲁肽是其代表药物。本文基于系统的文献检索,综述了利拉鲁肽和司美格鲁肽直接作用于肝肾(调控自噬、关键脂质代谢通路、胆固醇逆向转运等途径)、直接作用于脂肪组织(影响脂肪细胞增殖与分化、脂质代谢蛋白表达及基因转录)、通过中枢神经系统激活交感神经通路、调节肠道微生物群等降脂机制,还总结了其在2型糖尿病(T2DM)、超重等人群中的临床降脂证据。上述内容表明,GLP-1受体激动剂可通过作用于多个组织或系统而发挥降脂作用,为深入阐明此类药物在血脂调节中的分子机制及挖掘潜在的临床应用新思路提供了重要依据。
Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel class of antidiabetic drugs that also possess lipid-lowering and cardiovascular protective effects, with liraglutide and semaglutide being their representative medications. Based on a systematic literature search, this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney (regulating autophagy, key lipid metabolism pathways, reverse cholesterol transport, etc.), direct actions on adipose tissue (affecting adipocyte proliferation and differentiation, expression of lipid metabolism proteins, and gene transcription), activation of sympathetic pathways through the central nervous system, and modulation of the gut microbiota. Additionally, it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus, overweight individuals, and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems, providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.
SPASOVSKI G , RROJI M , HRISTOV G , et al . A new hope on the horizon for kidney and cardiovascular protection with SGLT2 inhibitors,GLP-1 receptor agonists,and mineralocorticoid receptor antagonists in type 2 diabetic and chronic kidney disease patients [J ] . Metab Syndr Relat Disord , 2024 , 22 ( 3 ): 170 - 178 .
HONIGBERG M C , CHANG L S , MCGUIRE D K , et al . Use of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and cardiovascular disease:a review [J ] . JAMA Cardiol , 2020 , 5 ( 10 ): 1182 - 1190 .
CARUSO I , CIGNARELLI A , SORICE G P , et al . Cardiovascular and renal effectiveness of GLP-1 receptor agonists vs. other glucose-lowering drugs in type 2 diabetes:a systematic review and meta-analysis of real-world studies [J ] . Metabolites , 2022 , 12 ( 2 ): 183 .
SOLINI A , TRICÒ D , DEL PRATO S . Incretins and cardiovascular disease:to the heart of type 2 diabetes [J ] . Diabetologia , 2023 , 66 ( 10 ): 1820 - 1831 .
GUL U , AUNG T , MARTIN M , et al . A comprehensive review of the role of GLP-1 agonists in weight management and their effect on metabolic parameters such as blood glucose,cholesterol,and blood pressure [J ] . Cureus , 2024 , 16 ( 12 ): e76519 .
PI-SUNYER X , ASTRUP A , FUJIOKA K , et al . A randomized,controlled trial of 3.0 mg of liraglutide in weight management [J ] . N Engl J Med , 2015 , 373 ( 1 ): 11 - 22 .
CUI W Q , SATHYANARAYAN A , LOPRESTI M , et al . Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis [J ] . Autophagy , 2021 , 17 ( 3 ): 690 - 705 .
FANG Y Y , JI L L , ZHU C Y , et al . Liraglutide alleviates hepatic steatosis by activating the TFEB-regulated autophagy-lysosomal pathway [J ] . Front Cell Dev Biol , 2020 , 8 : 602574 .
FAN M L , JIANG H W , ZHANG Y Y , et al . Liraglutide enhances autophagy and promotes pancreatic β cell proli-feration to ameliorate type 2 diabetes in high-fat-fed and streptozotocin-treated mice [J ] . Med Sci Monit , 2018 , 24 : 2310 - 2316 .
ROSENSON R S , BREWER H B , Jr , DAVIDSON W S , et al . Cholesterol efflux and atheroprotection:advancing the concept of reverse cholesterol transport [J ] . Circulation , 2012 , 125 ( 15 ): 1905 - 1919 .
XIAO X , KENNELLY J P , FERRARI A , et al . Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis [J ] . Nat Metab , 2023 , 5 ( 1 ): 165 - 181 .
Jr. ROSKOSKI R , ERK1/2 MAP kinases:structure,function,and regulation [J ] . Pharmacol Res , 2012 , 66 ( 2 ): 105 - 143 .
WU Y R , SHI X Y , MA C Y , et al . Liraglutide improves lipid metabolism by enhancing cholesterol efflux associa-ted with ABCA1 and ERK1/2 pathway [J ] . Cardiovasc Diabetol , 2019 , 18 ( 1 ): 146 .
WU W X , WANG Y , SHAO X , et al . GLP-1RA improves diabetic renal injury by alleviating glomerular endothelial cells pyroptosis via RXRα/circ8411/miR-23a-5p/ABCA1 pathway [J ] . PLoS One , 2024 , 19 ( 12 ): e0314628 .
SHAO Y M , YUAN G H , ZHANG J Q , et al . Liraglutide reduces lipogenetic signals in visceral adipose of db/db mice with AMPK activation and Akt suppression [J ] . Drug Des Devel Ther , 2015 , 9 : 1177 - 1184 .
ZHANG N , LIU C , ZHANG Y , et al . Liraglutide regulates lipid metabolism via FGF21-LKB1-AMPK-ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice [J ] . Biochem Biophys Res Commun , 2021 , 548 : 120 - 126 .
REIS-BARBOSA P H , MARCONDES-DE-CASTRO I A , MARINHO T S , et al . The mTORC1/AMPK pathway plays a role in the beneficial effects of semaglutide(GLP-1 receptor agonist)on the liver of obese mice [J ] . Clin Res Hepatol Gastroenterol , 2022 , 46 ( 6 ): 101922 .
PERFIELD J W , 2nd , ORTINAU L C , PICKERING R T , et al . Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin-deficient ob/ob mice [J ] . J Obes , 2013 , 2013 : 296537 .
SOTO-CATALÁN M , OPAZO-RÍOS L , QUICENO H , et al . Semaglutide improves liver steatosis and de novo lipogenesis markers in obese and type-2-diabetic mice with metabolic-dysfunction-associated steatotic liver disease [J ] . Int J Mol Sci , 2024 , 25 ( 5 ): 2961 .
VENDRELL J , EL BEKAY R , PERAL B , et al . Study of the potential association of adipose tissue GLP-1 receptor with obesity and insulin resistance [J ] . Endocrinology , 2011 , 152 ( 11 ): 4072 - 4079 .
CHEN J C , ZHAO H C , MA X L , et al . GLP-1/GLP-1R signaling in regulation of adipocyte differentiation and lipogenesis [J ] . Cell Physiol Biochem , 2017 , 42 ( 3 ): 1165 - 1176 .
LI Y M , DU J Y , ZHU E D , et al . Liraglutide suppresses proliferation and induces adipogenic differentiation of 3T3-L1 cells via the Hippo-YAP signaling pathway [J ] . Mol Med Rep , 2018 , 17 ( 3 ): 4499 - 4507 .
ZHANG J M , YANG G C , LIU J B , et al . Glucagon-like peptide-1 analog liraglutide reduces fat deposition in chicken adipocytes [J ] . Poult Sci , 2024 , 103 ( 7 ): 103766 .
ZHU R Y , CHEN S C . Proteomic analysis reveals sema-glutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice [J ] . Front Endocrinol (Lausanne) , 2023 , 14 : 1095432 .
LI H , LIU G , WAN X Q , et al . The zinc finger and BTB domain containing protein ZBTB20 regulates plasma tri-glyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes [J ] . Hepatology , 2022 , 75 ( 5 ): 1169 - 1180 .
LI Y , GAO R , YANG Z Y , et al . Liraglutide modulates lipid metabolism via ZBTB20-LPL pathway [J ] . Life Sci , 2025 , 360 : 123267 .
NOGUEIRAS R , PÉREZ-TILVE D , VEYRAT-DUREBEX C , et al . Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity [J ] . J Neurosci , 2009 , 29 ( 18 ): 5916 - 5925 .
BEIROA D , IMBERNON M , GALLEGO R , et al . GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK [J ] . Diabetes , 2014 , 63 ( 10 ): 3346 - 3358 .
LOCKIE S H , HEPPNER K M , CHAUDHARY N , et al . Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling [J ] . Diabetes , 2012 , 61 ( 11 ): 2753 - 2762 .
ZHAO L , CHEN Y , XIA F Z , et al . A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota [J ] . Front Endocrinol (Lausanne) , 2018 , 9 : 233 .
DENG X L , MA J , SONG M T , et al . Effects of products designed to modulate the gut microbiota on hyperlipidaemia [J ] . Eur J Nutr , 2019 , 58 ( 7 ): 2713 - 2729 .
ZENG Y , WU Y F , ZHANG Q , et al . Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases [J ] . mBio , 2024 , 15 ( 1 ): e0203223 .
ZHAO L , QIU Y , ZHANG P P , et al . Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet [J ] . Front Nutr , 2022 , 9 : 1048693 .
MAO T H , ZHANG C X , YANG S , et al . Semaglutide alters gut microbiota and improves NAFLD in db/db mice [J ] . Biochem Biophys Res Commun , 2024 , 710 : 149882 .
RODBARD H W , LINGVAY I , REED J , et al . Semaglutide added to basal insulin in type 2 diabetes(SUSTAIN 5):a randomized,controlled trial [J ] . J Clin Endocrinol Metab , 2018 , 103 ( 6 ): 2291 - 2301 .
DAHL K , BROOKS A , ALMAZEDI F , et al . Oral sema-glutide improves postprandial glucose and lipid metabolism,and delays gastric emptying,in subjects with type 2 diabetes [J ] . Diabetes Obes Metab , 2021 , 23 ( 7 ): 1594 - 1603 .
LOOMBA R , ABDELMALEK M F , ARMSTRONG M J , et al . Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis:a randomised,placebo-controlled phase 2 trial [J ] . Lancet Gastroenterol Hepatol , 2023 , 8 ( 6 ): 511 - 522 .
SVANE M S , JOHANNESEN H H , HANSEN A E , et al . Four weeks treatment with the GLP-1 receptor analogue liraglutide lowers liver fat and concomitantly circulating glucagon in individuals with overweight [J ] . Int J Obes(Lond) , 2022 , 46 ( 11 ): 2058 - 2062 .
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