体能科学

运动诱导脂肪组织巨噬细胞表型变化对胰岛素抵抗的影响

谢超

摘要


糖尿病(DM)是以糖脂代谢紊乱为主要特征的代谢障碍性疾病,2型糖尿病(T2DM)占90%以上,其主要表征为胰岛素抵抗(IR)。肥胖状态下,脂肪细胞会分泌趋化因子(MCP-I),吸引单核细胞进入脂肪组织和肝脏,极化为促炎巨噬细胞M1,M1巨噬细胞上调促炎介质的表达,如IL-6、TNF-α等,通过MAPK-JNK通路作用于脂肪细胞诱导IR。运动作为一种预防和治疗T2DM的非药物干预手段,可通过调节巨噬细胞表型,降低促炎介质TNF-α、IL-6表达水平,抑制脂肪组织MAPK-JNK通路活性改善胰岛素抵抗,从而延缓T2DM病理进程。

关键词


2型糖尿病;巨噬细胞;促炎介质;TNF-α;IL-6;胰岛素抵抗

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参考


徐兰婷.异补骨脂色烯查尔酮改善3T3-L1脂肪细胞胰岛素抵抗作用机制研究[C].郑州:河南大学,2020.

Gasmi A, Noor S, Menzel A, et al. Obesity and insulin resistance: associations with chronic inflammation, genetic and epigenetic factors[J].Current Medicinal Chemistry,2021,28(4):800-826.

Qatanani M, Lazar M A. Mechanisms of obesity-associated insulin resistance: many choices on the menu[J].Genes & development,2007,21(12):1443-1455.

Olefsky J M, Glass C K. Macrophages, inflammation, and insulin resistance[J].Annual review of physiology,2010(72):219-246.

Nagareddy P R, Kraakman M, Masters S L, et al. Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity[J].Cell metabolism,2014,19(5):821-835.

Weisberg S P, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue[J].The Journal of clinical investigation,2003,112(12):1796-1808.

Swarbrick M M, Havel P J. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans[J].Metabolic syndrome and related disorders,2008,6(2):87-102.

Abate N, S Sallam H, Rizzo M, et al. Resistin: an inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome[J].Current pharmaceutical design,2014,20(31):4961-4969.

Kirwan J P, Sacks J, Nieuwoudt S. The essential role of exercise in the management of type 2 diabetes[J].Cleveland Clinic journal of medicine,2017,84(7):15.

俞莹莹,赵彦,谭朝文,等.运动结合药物对糖尿病小鼠骨骼肌炎症的影响[J].糖尿病新世界,2021(11):15-18.

Burhans M S, Hagman D K, Kuzma J N, et al. Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus[J].Comprehensive Physiology,2018,9(1):1.

Kanda H, Tateya S, Tamori Y, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity[J].The Journal of clinical investigation,2006,116(6):1494-1505.

Gao Z, Hwang D, Bataille F, et al. Serine phosphorylation of insulin receptor substrate 1 by inhibitor κB kinase complex[J].Journal of Biological Chemistry,2002,277(50):48115-48121.

Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance[J].Nature,2002,420(6913):333-336.

Ozes O N, Akca H, Mayo L D, et al. A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1[J].Proceedings of the National Academy of Sciences,2001,98(8):4640-4645.

Bastard J P, Maachi M, Van Nhieu J T, et al. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro[J].The Journal of Clinical Endocrinology & Metabolism,2002,87(5):2084-2089.

Han M S, Jung D Y, Morel C, et al. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation[J].Science,2013,339(6116):218-222.

Maeda N, Takahashi M, Funahashi T, et al. PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein[J].Diabetes,2001,50(9):2094-2099.

Ruan H, Dong L Q. Adiponectin signaling and function in insulin target tissues[J]. Journal of molecular cell biology,2016,8(2):101-109.

Liang W, Qi Y, Yi H, et al. The Roles of Adipose Tissue Macrophages in Human Disease[J].Frontiers in Immunology,2022(13):908749.

Zatterale F, Longo M, Naderi J, et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes[J].Frontiers in physiology,2020:1607.

窦爱霞;陆伦根.脂肪性肝病形成中的免疫因素[J].内科理论与实践,2006(1):63-67.

Weisberg S P, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding[J].The Journal of clinical investigation,2006,116(1):115-124.

Kershaw E E, Flier J S. Adipose tissue as an endocrine organ[J]. The Journal of Clinical Endocrinology & Metabolism,2004,89(6):2548-2556.

徐兰婷.异补骨脂色烯查尔酮改善3T3-L1脂肪细胞胰岛素抵抗作用机制研究[C].郑州:河南大学,2020.

Lumeng C N, Bodzin J L, Saltiel A R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization[J].The Journal of clinical investigation,2007,117(1):175-184.

Liu R, Nikolajczyk B S. Tissue immune cells fuel obesity-associated inflammation in adipose tissue and beyond[J].Frontiers in immunology,2019(10):1587.

Weisberg S P, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue[J].The Journal of clinical investigation,2003,112(12):1796-1808.

刘云.NAFLD中医组方规律分析和中医证候特征调查及葱白提取物治疗NAFLD大鼠的机制研究[C].武汉:湖北中医药大学,2021.

Gentek R, Molawi K, Sieweke M H. Tissue macrophage identity and self‐renewal[J]. Immunological reviews,2014,262(1):56-73.

Mills C. M1 and M2 macrophages: oracles of health and disease[J]. Critical Reviews™ in Immunology,2012,32(6).

Julian V, Thivel D, Miguet M, et al. Eccentric cycling is more efficient in reducing fat mass than concentric cycling in adolescents with obesity[J].Scandinavian Journal of Medicine & Science in Sports,2019,29(1):4-15.

Liu G, Yang H. Modulation of macrophage activation and programming in immunity[J]. Journal of cellular physiology,2013,228(3):502-512.

Shaul M E, Bennett G, Strissel K J, et al. Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet–induced obesity in mice[J].Diabetes,2010,59(5):1171-1181.

Gordon S, Taylor P R. Monocyte and macrophage heterogeneity[J].Nature reviews immunology,2005,5(12):953-964.

Thorp E, Subramanian M, Tabas I. The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis[J]. European journal of immunology,2011,41(9):2515-2518.

Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance[J]. Nature Reviews Endocrinology,2012,8(12):709-716.

Lumeng C N, Saltiel A R. Inflammatory links between obesity and metabolic disease[J]. The Journal of clinical investigation,2011,121(6):2111-2117.

Xu H, Barnes G T, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance[J].The Journal of clinical investigation,2003,112(12):1821-1830.

Püschel G P, Klauder J, Henkel J. Macrophages, low-grade inflammation, insulin resistance and hyperinsulinemia: A mutual ambiguous relationship in the development of metabolic diseases[J]. Journal of Clinical Medicine,2022,11(15):4358.

Chen J, Sun Z, Jin M, et al. Inhibition of AGEs/RAGE/Rho/ROCK pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway[J]. Journal of neuroimmunology,2017(305):108-114.

Hofmann C, Lorenz K, Braithwaite S S, et al. Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance[J].Endocrinology,1994,134(1):264-270.

Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance[J].Nature,2002,420(6913):333-336.

Akash M S H, Rehman K, Liaqat A. Tumor necrosis factor‐alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus[J].Journal of cellular biochemistry,2018,119(1):105-110.

Olson A L. Regulation of GLUT4 and insulin-dependent glucose flux[J].International Scholarly Research Notices,2012(2012).

Stouthard J M, Romijn J A, Van der Poll T, et al. Endocrinologic and metabolic effects of interleukin-6 in humans[J].American Journal of Physiology-Endocrinology And Metabolism,1995,268(5):813-819.

Senn J J, Klover P J, Nowak I A, et al. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes[J]. Journal of Biological Chemistry,2003,278(16):13740-13746.

Rehman K, Akash M S H, Liaqat A, et al. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus[J].Critical Reviews™ in Eukaryotic Gene Expression,2017,27(3).

Zeyda M, Stulnig T M. Obesity, inflammation, and insulin resistance–a mini-review[J]. Gerontology,2009,55(4):379-386.

Greenberg A S, McDaniel M L. Identifying the links between obesity, insulin resistance and β‐cell function: potential role of adipocyte‐derived cytokines in the pathogenesis of type 2 diabetes[J].European journal of clinical investigation,2002(32):24-34.

翁惊凡;郭航远;池菊芳.JNK信号通路在糖尿病心肌病中的作用研究进展[J].浙江医学,2020(15):1664-1668.

Hu S, Ma S, Li X, et al. Relationships of SLC2A4, RBP4, PCK1, and PI3K gene polymorphisms with gestational diabetes mellitus in a Chinese population[J].BioMed Research International,2019(2019).

Solinas G, Becattini B. JNK at the crossroad of obesity, insulin resistance, and cell stress response[J].Molecular metabolism,2017,6(2):174-184.

Torkamandi S, Bastami M, Ghaedi H, et al. MAP3K1 may be a promising susceptibility gene for type 2 diabetes mellitus in an Iranian population[J].International Journal of Molecular and Cellular Medicine,2016,5(3):134.

Shoelson S E, Lee J, Goldfine A B. Inflammation and insulin resistance[J]. The Journal of clinical investigation,2006,116(7):1793-1801.

Van Dyken S J, Locksley R M. Interleukin-4-and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease[J].Annual review of immunology,2013(31):317-343.

吕甜甜.白细胞介素-10与系统性红斑狼疮相关性的分子流行病学研究[C].合肥:安徽医科大学,2018.

Saraiva M, O'garra A. The regulation of IL-10 production by immune cells[J].Nature reviews immunology,2010,10(3):170-181.

Dhingra S, Bagchi A K, Ludke A L, et al. Akt regulates IL-10 mediated suppression of TNFα-induced cardiomyocyte apoptosis by upregulating Stat3 phosphorylation[J].PLoS One,2011,6(9):25009.

Hong E G, Ko H J, Cho Y R, et al. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle[J].Diabetes,2009,58(11):2525-2535.

李敏,袁晓丹,戴霞,等.不同运动方式对糖尿病前期患者2型糖尿病风险的影响:一项为期2年的前瞻性随机对照研究[J].中华内分泌代谢杂志,2021,37(10):895-904.

常凤,杜可新,李国平.不同运动方案对中年2型糖尿病患者健康体适能促进效果的临床疗效观察[J].中国康复医学杂志,2018(5):559-564.

刘倩,李冬静,李艳丽,等.有氧运动联合抗阻运动在2型糖尿病病人中的应用[J].护理研究,2021,35(9):1670-1672.

Liu S X, Zheng F, Xie K L,et al.Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis[J].Molecular Therapy-Nucleic Acids,2019(18):34-44.

牟川,陈庆果.有氧运动抑制胰岛素抵抗小鼠肝脏糖异生及FNDC5/Irisin调控研究[J].西安体育学院学报,2022,39(3):345-354.

Li N, Shi H, Guo Q, et al. Aerobic Exercise Prevents Chronic Inflammation and Insulin Resistance in Skeletal Muscle of High-Fat Diet Mice[J].Nutrients,2022,14(18):3730.

Gopalan V, Yaligar J, Michael N, et al. A 12-week aerobic exercise intervention results in improved metabolic function and lower adipose tissue and ectopic fat in high-fat diet fed rats[J].Bioscience Reports,2021,41(1).

税晓平,曹艳霞,李顺昌,等.不同运动对糖尿病大鼠周围神经结构功能的影响及机制[J].中国运动医学杂志,2018(10):857-864.

高晋晋,徐晓阳,王欢,等.不同运动对胰岛素抵抗大鼠肝脏脂肪酸代谢的影响及机制探讨[J].山东体育科技,2023,45(1):52-56.

Mai K, Klug L, Rakova N, et al. Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial[J].International Journal of Obesity,2020,44(5):1119-1128.

Cheng F, Dun Y, Cheng J, et al. Exercise activates autophagy and regulates endoplasmic reticulum stress in muscle of high-fat diet mice to alleviate insulin resistance[J].Biochemical and Biophysical Research Communications,2022(601):45-51.

Kawanishi N, Yano H, Yokogawa Y, et al. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice[J].Exercise immunology review,2010(16).

Luo W, Ai L, Wang B, et al. Eccentric exercise and dietary restriction inhibits M1 macrophage polarization activated by high-fat diet-induced obesity[J].Life sciences,2020(243):117246.

Kawanishi N, Mizokami T, Yano H, et al. Exercise attenuates M1 macrophages and CD8+ T cells in the adipose tissue of obese mice[J].Med Sci Sports Exerc,2013,45(9):1684-93.

Wang Y, Guo Y, Xu Y, et al. HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice[J].Metabolites,2022,13(1):14.

Kolahdouzi S, Talebi-Garakani E, Hamidian G, et al. Exercise training prevents high-fat diet-induced adipose tissue remodeling by promoting capillary density and macrophage polarization[J].Life sciences,2019(220):32-43.

Oliveira A G, Araujo T G, Carvalho B M, et al. Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet‐induced obese rats[J]. Obesity,2013,21(12):2545-2556.

Shanaki M, Khosravi M, Khoshdooni-Farahani A, et al. High-intensity interval training reversed high-fat diet–induced M1-macrophage polarization in rat adipose tissue via inhibition of NOTCH signaling[J].Journal of Inflammation Research,2020:165-174.

Wang J, Polaki V, Chen S, et al. Exercise improves endothelial function associated with alleviated inflammation and oxidative stress of perivascular adipose tissue in type 2 diabetic mice[J].Oxidative Medicine and Cellular Longevity,2020(2020).

朱光辉,李常青,李欣.规律性有氧运动对成年人血浆白介素-6水平影响的Meta分析[J].体育科学,2015(10):90-97.

Song M J, Kim K H, Yoon J M, et al. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes[J].Biochemical and biophysical research communications,2006,346(3):739-745.

贺强,季浏.一次急性耐力游泳运动对DIO小鼠脂肪组织巨噬细胞介导的慢性炎症的影响[J].北京体育大学学报,2016(2):61-68.

王海涛,李海洲,李立卓,等.大强度运动后低氧对大鼠炎症反应和十二指肠铁吸收蛋白的影响[J].中国运动医学杂志,2013(4):32.

Pedersen B K. Anti‐inflammatory effects of exercise: role in diabetes and cardiovascular disease[J].European journal of clinical investigation,2017,47(8):600-611.




DOI: https://doi.org/10.33142/jscs.v3i5.10173

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