脂蛋白相关磷脂酶A2 (Lp-PLA2)与肥胖合并2型糖尿病关系的研究进展
Research Progress on the Relationship between Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) and Obesity Complicated with Type 2 Diabetes Mellitus
DOI: 10.12677/acm.2026.1651984, PDF,   
作者: 王茂歌, 胡三元*:山东第一医科大学第一附属医院普通外科,山东 济南
关键词: 肥胖2型糖尿病脂蛋白相关磷脂酶A2手术治疗Obesity Type 2 Diabetes Mellitus Lipoprotein-Associated Phospholipase A2 Surgical Treatment
摘要: 肥胖与2型糖尿病(T2DM)的全球发病率呈持续上升趋势,二者共病的核心机制为慢性低度炎症与胰岛素抵抗,已成为重大公共卫生问题。脂蛋白相关磷脂酶A2 (Lp-PLA2)作为血管特异性炎症标志物,在脂质代谢、炎症反应调控中发挥关键作用,其表达水平与肥胖、T2DM的发病及并发症进展密切相关。本文系统综述Lp-PLA2的生物学功能及结构特点,阐述肥胖与T2DM的病理生理关联,深入分析Lp-PLA2在肥胖合并T2DM中的作用机制,探讨其与减重手术治疗疗效的相关性,并展望未来研究方向,为肥胖合并T2DM的防治提供新的思路与理论依据。
Abstract: The global incidence of obesity and type 2 diabetes mellitus (T2DM) has been on a steady rise, and the core mechanisms underlying their comorbidity are chronic low-grade inflammation and insulin resistance, which have become a major public health concern. Lipoprotein-associated phospholipase A2 (Lp-PLA2), as a vascular-specific inflammatory marker, plays a pivotal role in lipid metabolism and the regulation of inflammatory responses. Its expression level is closely associated with the onset of obesity and T2DM as well as the progression of their complications. This paper systematically reviews the biological functions and structural characteristics of Lp-PLA2, elaborates on the pathophysiological relationship between obesity and T2DM, deeply analyzes the mechanism of action of Lp-PLA2 in obesity complicated with T2DM, discusses its correlation with the therapeutic efficacy of bariatric surgery, and prospects future research directions, aiming to provide new ideas and theoretical basis for the prevention and treatment of obesity complicated with T2DM.
文章引用:王茂歌, 胡三元. 脂蛋白相关磷脂酶A2 (Lp-PLA2)与肥胖合并2型糖尿病关系的研究进展[J]. 临床医学进展, 2026, 16(5): 1808-1816. https://doi.org/10.12677/acm.2026.1651984

参考文献

[1] Hariharan, R., Odjidja, E.N., Scott, D., Shivappa, N., Hébert, J.R., Hodge, A., et al. (2022) The Dietary Inflammatory Index, Obesity, Type 2 Diabetes, and Cardiovascular Risk Factors and Diseases. Obesity Reviews, 23, e13349. [Google Scholar] [CrossRef] [PubMed]
[2] Huang, F., Wang, K. and Shen, J. (2019) Lipoprotein-Associated Phospholipase A2: The Story Continues. Medicinal Research Reviews, 40, 79-134. [Google Scholar] [CrossRef] [PubMed]
[3] Paik, J.K., Kim, M., Kim, M., Yen, Y., Ahn, H.Y., Lee, S., et al. (2015) Circulating Lp-PLA2 Activity Correlates with Oxidative Stress and Cytokines in Overweight/obese Postmenopausal Women Not Using Hormone Replacement Therapy. AGE, 37, Article No. 32. [Google Scholar] [CrossRef] [PubMed]
[4] Li, D., Qian, Y., Wan, L., Zhang, K., Song, L., Zhang, X., et al. (2026) Lipoprotein-associated Phospholipase A2 (lp-Pla2): A Key Hub Linking Lipid Metabolism and Immune Inflammation. Frontiers in Immunology, 17, Article 1705738. [Google Scholar] [CrossRef
[5] Zalewski, A., Nelson, J.J., Hegg, L. and Macphee, C. (2006) Lp-PLA2: A New Kid on the Block. Clinical Chemistry, 52, 1645-1650. [Google Scholar] [CrossRef] [PubMed]
[6] Racherla, S. and Arora, R. (2012) Utility of Lp-PLA2 in Lipid-Lowering Therapy. American Journal of Therapeutics, 19, 115-120. [Google Scholar] [CrossRef] [PubMed]
[7] Ait-Oufella, H., Mallat, Z. and Tedgui, A. (2014) Lp-PLA2 et sPLA2: Cardiovascular Biomarkers. Médecine/Sciences, 30, 526-531. [Google Scholar] [CrossRef] [PubMed]
[8] Bonnefont-Rousselot, D. (2016) Lp-PLA2, a Biomarker of Vascular Inflammation and Vulnerability of Atherosclerosis Plaques. Annales Pharmaceutiques Francaises, 74, 190-197.
[9] Hotamisligil, G.S. (2006) Inflammation and Metabolic Disorders. Nature, 444, 860-867. [Google Scholar] [CrossRef] [PubMed]
[10] Karakas, M. and Koenig, W. (2010) Lp-PLA2 Inhibition—The Atherosclerosis Panacea? Pharmaceuticals, 3, 1360-1373. [Google Scholar] [CrossRef] [PubMed]
[11] Xepapadaki, E., Nikdima, I., Sagiadinou, E.C., Zvintzou, E. and Kypreos, K.E. (2021) HDL and Type 2 Diabetes: The Chicken or the Egg? Diabetologia, 64, 1917-1926. [Google Scholar] [CrossRef] [PubMed]
[12] da Silva, J.F., Alves, J.V., Silva-Neto, J.A., Costa, R.M., Neves, K.B., Alves-Lopes, R., et al. (2021) Lysophosphatidylcholine Induces Oxidative Stress in Human Endothelial Cells via NOX5 Activation—Implications in Atherosclerosis. Clinical Science, 135, 1845-1858. [Google Scholar] [CrossRef] [PubMed]
[13] Yuan, Z., Li, H., Ruan, B.X., Huang, H., Li, Y. and Wang, J. (2026) Macrophage‐Derived Galectin‐3 Contributes to Pyroptosis, Apoptosis and Necroptosis through TLR4/MyD88/NF‐κB/NLRP3 during Atherosclerosis. Clinical and Translational Medicine, 16, e70637. [Google Scholar] [CrossRef
[14] Li, N.N., Xiang, S.Y., Huang, X.X., et al. (2021) Network Pharmacology-Based Exploration of Therapeutic Mechanism of Liu-Yu-Tang in Atypical Antipsychotic Drug-Induced Metabolic Syndrome. Computers in Biology and Medicine, 134, Article 104452. [Google Scholar] [CrossRef] [PubMed]
[15] Ramirez, A.V.G., Filho, D.R. and de Sá, L.B.P.C. (2021) Melatonin and Its Relationships with Diabetes and Obesity: A Literature Review. Current Diabetes Reviews, 17, e07262018413. [Google Scholar] [CrossRef] [PubMed]
[16] Babu, S., Dash, I., Badrachalam, R., et al. (2023) An Update on Diagnosis and Therapeutics for Type-2 Diabetes Mellitus. Bioinformation, 19, 295-298. [Google Scholar] [CrossRef] [PubMed]
[17] Lempesis, I.G. and Georgakopoulou, V.E. (2023) Physiopathological Mechanisms Related to Inflammation in Obesity and Type 2 Diabetes Mellitus. World Journal of Experimental Medicine, 13, 7-16. [Google Scholar] [CrossRef] [PubMed]
[18] 卢冬磊, 杨风英, 冯展鹏, 等. 同期训练可改善伴有超重或肥胖2型糖尿病患者的健康效应: 一项Meta分析[J/OL]. 中国全科医学, 1-13.
http://kns--cnki--net--https.cnki.qfsy.qfclo.com:7002/kcms2/article/abstract?v=yLAonKG4u-SeMgjs4aQWemJGBXfiJxBMQGkYQ8d-XP27i7vqs83q56yUPAeR82HmA3VR7az1xYqDoQ8LHmgJ9q2CS-WEHGgLUR3ZtX9JKgH2SggqIROReT8SMdqx057pCHYetd_zAOUvmNLC6rpJ4m--vibfrRTWKX045WvaAUZC0LRYRTw-hA==&uniplatform=NZKPT&language=CHS, 2024-09-10.
[19] Kwaifa, I.K., Bahari, H., Yong, Y.K. and Noor, S.M. (2020) Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications. Biomolecules, 10, Article 291. [Google Scholar] [CrossRef] [PubMed]
[20] Lp-PLA(2) Studies Collaboration, Thompson, A., Gao, P., et al. (2010) Lipoprotein-Associated Phospholipase A(2) and Risk of Coronary Disease, Stroke, and Mortality: Collaborative Analysis of 32 Prospective Studies. The Lancet, 375, 1536-1544.
[21] Macphee, C., Benson, G.M., Shi, Y. and Zalewski, A. (2005) Lipoprotein-Associated Phospholipase A2: A Novel Marker of Cardiovascular Risk and Potential Therapeutic Target. Expert Opinion on Investigational Drugs, 14, 671-679. [Google Scholar] [CrossRef] [PubMed]
[22] Mohler, E.R., Ballantyne, C.M., Davidson, M.H., Hanefeld, M., Ruilope, L.M., Johnson, J.L., et al. (2008) The Effect of Darapladib on Plasma Lipoprotein-Associated Phospholipase A2 Activity and Cardiovascular Biomarkers in Patients with Stable Coronary Heart Disease or Coronary Heart Disease Risk Equivalent: The Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Journal of the American College of Cardiology, 51, 1632-1641. [Google Scholar] [CrossRef] [PubMed]
[23] Jackisch, L., Kumsaiyai, W., Moore, J.D., Al-Daghri, N., Kyrou, I., Barber, T.M., et al. (2018) Differential Expression of Lp-PLA2 in Obesity and Type 2 Diabetes and the Influence of Lipids. Diabetologia, 61, 1155-1166. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, G.H., Jin, J., Liu, Y.Q., et al. (2021) The Changes of Lp-PLA2 in Patients with Gestational Diabetes and Its Clinical Significance. Medicine, 100, e26786. [Google Scholar] [CrossRef] [PubMed]
[25] 凌静, 黄龑, 姜月, 等. 人血浆脂蛋白相关磷脂酶A2、同型半胱氨酸和血脂与不同肥胖类型的关系[J]. 浙江医学, 2022, 44(1): 72-75.
[26] Clark, K., Sharp, S., Womack, C.J., Kurti, S.P. and Hargens, T.A. (2022) Increased Sedentary Time and Decreased Physical Activity Increases Lipoprotein Associated Phospholipase A2 in Obese Individuals. Nutrition, Metabolism and Cardiovascular Diseases, 32, 1703-1710. [Google Scholar] [CrossRef] [PubMed]
[27] Martin, M., Gaete, L., Tetzlaff, W., Ferraro, F., Lozano Chiappe, E., Botta, E.E., et al. (2022) Vascular Inflammation and Impaired Reverse Cholesterol Transport and Lipid Metabolism in Obese Children and Adolescents. Nutrition, Metabolism and Cardiovascular Diseases, 32, 258-268. [Google Scholar] [CrossRef] [PubMed]
[28] Wang, J., Yang, S. and Zhao, L. (2024) Association of High-Sensitivity C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 with Metabolically Unhealthy Phenotype: A Cross Sectional Study. Journal of Inflammation Research, 17, 81-90. [Google Scholar] [CrossRef] [PubMed]
[29] Detopoulou, P., Nomikos, T., Fragopoulou, E., Panagiotakos, D.B., Pitsavos, C., Stefanadis, C., et al. (2009) Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Activity, Platelet-Activating Factor Acetylhydrolase (PAF-AH) in Leukocytes and Body Composition in Healthy Adults. Lipids in Health and Disease, 8, Article No. 19. [Google Scholar] [CrossRef] [PubMed]
[30] De Stefano, A., Mannucci, L., Tamburi, F., Cardillo, C., Schinzari, F., Rovella, V., et al. (2019) Lp-PLA2, a New Biomarker of Vascular Disorders in Metabolic Diseases. International Journal of Immunopathology and Pharmacology, 33, Article 2058738419827154. [Google Scholar] [CrossRef] [PubMed]
[31] Wolf, D. and Ley, K. (2019) Immunity and Inflammation in Atherosclerosis. Circulation Research, 124, 315-327. [Google Scholar] [CrossRef] [PubMed]
[32] Zhang, S.Y., Dong, Y.Q., Wang, P., et al. (2018) Adipocyte-Derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance. EBioMedicine, 31, 202-216. [Google Scholar] [CrossRef] [PubMed]
[33] Pizzuto, M., Pelegrin, P. and Ruysschaert, J. (2022) Lipid-Protein Interactions Regulating the Canonical and the Non-Canonical NLRP3 Inflammasome. Progress in Lipid Research, 87, Article 101182. [Google Scholar] [CrossRef] [PubMed]
[34] Chen, Y., Li, J., Shi, J., Ning, D., Feng, J., Lin, W., et al. (2022) Ipriflavone Suppresses NLRP3 Inflammasome Activation in Host Response to Biomaterials and Promotes Early Bone Healing. Journal of Clinical Periodontology, 49, 814-827. [Google Scholar] [CrossRef] [PubMed]
[35] Motykova, E., Zlatohlavek, L., Prusikova, M., et al. (2011) Lifestyle Modification Induced Weight Loss and Changes of Cardiometabolic Risk Factors Including Lowering of Inflammatory Response in Obese Children. Neuro Endocrinology Letters, 32, 55-59.
[36] 吴敏, 颜申姬, 杨联君, 等. 妊娠期糖尿病患者血清Lp-PLA2、P-LAP水平与糖脂代谢指标的相关性分析[J]. 中国医学创新, 2022, 19(11): 10-13.
[37] 何廉旗, 周进, 于欣, 等. 血清Lp-PLA2、sST2和NT-proBNP对ACS合并糖尿病患者短期预后的临床预测价值[J]. 重庆医学, 2022, 51(15): 2561-2565.
[38] Garg, S., Madhu, S. and Suneja, S. (2015) Lipoprotein Associated Phospholipase A2 Activity & Its Correlation with Oxidized LDL & Glycaemic Status in Early Stages of Type-2 Diabetes Mellitus. Indian Journal of Medical Research, 141, 107-114. [Google Scholar] [CrossRef] [PubMed]
[39] Chen, Y., Wang, S., Li, J., Fu, Y., Chen, P., Liu, X., et al. (2024) The Relationships between Biological Novel Biomarkers Lp-PLA2 and CTRP-3 and CVD in Patients with Type 2 Diabetes Mellitus. Journal of Diabetes, 16, e13574. [Google Scholar] [CrossRef] [PubMed]
[40] Feng, F., Chen, Y., Wang, G., Huang, P., Zhu, Q. and Zhou, B. (2022) Correlation of Serum CysC, IMA, and LP-PLA2 Levels with Type 2 Diabetes Mellitus Patients with Lower Extremity Atherosclerotic Occlusive Disease. Frontiers in Surgery, 9, Article 846470. [Google Scholar] [CrossRef] [PubMed]
[41] Ren, J., Chang, M., Song, S., Zhao, R., Xing, X. and Chang, X. (2022) Predictive Value of Serum Lipoprotein-Associated Phospholipase A2 for Type 2 Diabetes Mellitus Complicated with Metabolic Syndrome in Elderly Patients. Clinical Laboratory, 68. [Google Scholar] [CrossRef] [PubMed]
[42] Zhang, Z., Qian, X., Sun, Z., Cheng, C. and Gu, M. (2024) Association between Lipoprotein-Associated Phospholipase A2 and 25-Hydroxy-Vitamin D on Early Stage Diabetic Kidney Disease in Patients with Type-2 Diabetes Mellitus. Heliyon, 10, e35635. [Google Scholar] [CrossRef] [PubMed]
[43] Castagneto Gissey, L., Casella Mariolo, J.R. and Mingrone, G. (2016) How to Choose the Best Metabolic Procedure? Current Atherosclerosis Reports, 18, Article No. 43. [Google Scholar] [CrossRef] [PubMed]
[44] Chiappe, E.L., Martin, M., Iglesias Molli, A., Millan, A., Tetzlaff, W., Botta, E., et al. (2021) Effect of Roux-En-Y Gastric Bypass on Lipoprotein Metabolism and Markers of HDL Functionality in Morbid Obese Patients. Obesity Surgery, 31, 1092-1098. [Google Scholar] [CrossRef] [PubMed]
[45] Julve, J., Pardina, E., Pérez-Cuéllar, M., Ferrer, R., Rossell, J., Baena-Fustegueras, J.A., et al. (2014) Bariatric Surgery in Morbidly Obese Patients Improves the Atherogenic Qualitative Properties of the Plasma Lipoproteins. Atherosclerosis, 234, 200-205. [Google Scholar] [CrossRef] [PubMed]
[46] Ference, B.A., Robinson, J.G., Brook, R.D., Catapano, A.L., Chapman, M.J., Neff, D.R., et al. (2016) Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. New England Journal of Medicine, 375, 2144-2153. [Google Scholar] [CrossRef] [PubMed]
[47] Grundy, S.M., Stone, N.J., Bailey, A.L., et al. (2019) 2018 AHA/ACC/AACVPR/AAPA/ABC /ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 139, e1046-e1081.