中药调控3T3-L1脂肪细胞增殖、分化和糖脂代谢的研究进展

doi:10.13481/j.1671-587x.20200435

摘要/Abstract

摘要： 脂肪细胞的增殖、分化与肥胖和胰岛素抵抗等代谢性疾病有密切的关系，而传统中药在治疗各种疾病方面积累了丰富的实践经验。近年来许多研究以证明传统中药可通过调控脂肪细胞数量以及大小来改善某些代谢性疾病。脂肪细胞的形成是成纤维细胞样前脂肪细胞向成熟脂肪细胞转变的过程，脂肪的生成即是脂质的积累，需要依次激活众多转录因子。3T3-L1前脂肪细胞系是建立成熟脂肪细胞模型最为常用的细胞系之一，转变为成熟的脂肪细胞需要经历有丝分裂克隆扩增（MCE）阶段、终末分化阶段和分化为成熟脂肪细胞阶段。脂质代谢紊乱是引起肥胖和胰岛素抵抗等疾病的原因，许多中药通过抑制前脂肪细胞的增殖和分化，减少脂质的积累，改善或预防肥胖。胰岛素抵抗是2型糖尿病的早期症状、核心特征和主要发病机制之一。中药通过调控糖脂代谢，促进胰岛素信号转导，提高胰岛素敏感性，从而改善胰岛素抵抗。现总结近年来各种中药单体、单方或复方对3T3-L1细胞分化和代谢影响的研究，以及中药治疗肥胖和胰岛素抵抗等代谢性疾病机制的研究进展，旨在为传统中药治疗此类疾病提供参考。

关键词: 3T3-L1脂肪细胞, 细胞增殖, 细胞分化, 糖脂代谢, 中药治疗

中图分类号:

R285.5

高海云, 徐闯, 崔一喆, 王秋菊. 中药调控3T3-L1脂肪细胞增殖、分化和糖脂代谢的研究进展[J]. 吉林大学学报(医学版), 2020, 46(04): 881-887.

参考文献

[1] WORLD HEALTH ORGANIZATION. 10 facts on obesity[EB/OL].[2019-09-11].https://www.who.int/features/factfiles/obesity/zh/.
[2] FLOYD Z E, GAWRONSKA-KOZAK B, TAM C S, et al. Mechanisms of metabolism, aging and obesity[J]. Biochimie, 2016, 124:1-2.
[3] LEE S J, SHIN S W. Mechanisms, pathophysiology, and management of obesity[J]. N Engl J Med, 2017, 376(15):1490-1492.
[4] KOPELMAN P G. Obesity as a medical problem[J]. Nature, 2000, 404(6778):635-643.
[5] CHANG E, KIM C Y. Natural products and obesity:a focus on the regulation of mitotic clonal expansion during adipogenesis[J]. Molecules, 2019, 24(6):E1157.
[6] XU L Y, ZHAO W J, WANG D M, et al. Chinese medicine in the battle against obesity and metabolic diseases[J]. Front Physiol, 2018, 9:850.
[7] 杨大伟, 王民登, 吴标良, 等. 胰岛素抵抗的研究进展[J]. 右江医学, 2019, 47(6):472-475.
[8] YEE H Y, 杨晶晶, 万毅刚, 等. 胰岛素抵抗的分子机制及中药的干预作用[J]. 中国中药杂志, 2019, 44(7):1289-1294.
[9] SCOTT R E, FLORINE D L, WILLE J J J R, et al. Coupling of growth arrest and differentiation at a distinct state in the G₁ phase of the cell cycle:GD[J]. Proc Natl Acad Sci U S A, 1982, 79(3):845-849.
[10] PAIRAULT J, GREEN H. A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker[J]. Proc Natl Acad Sci U S A, 1979, 76(10):5138-5142.
[11] MACDOUGALD O A, MANDRUP S. Adipogenesis:forces that tip the scales[J]. Trends Endocrinol Metab, 2002, 13(1):5-11.
[12] WU J H, SRINIVASAN S V, NEUMANN J C, et al. The KLF2 transcription factor does not affect the formation of preadipocytes but inhibits their differentiation into adipocytes[J]. Biochemistry, 2005, 44(33):11098-11105.
[13] TONTONOZ P, HU E, SPIEGELMAN B M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor[J]. Cell, 1994, 79(7):1147-1156.
[14] TANG Q Q, ZHANG J W, DANIEL LANE M.Sequential gene promoter interactions by C/EBPβ, C/EBPα, and PPARγ during adipogenesis[J]. Biochem Biophys Res Commun, 2004, 318(1):213-218.
[15] LONDOS C, BRASAEMLE D L, SCHULTZ C J, et al. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells[J]. Semin Cell Dev Biol, 1999, 10(1):51-58.
[16] KOERNER A, KRATZSCH J, KIESS W. Adipocytokines:leptin:the classical, resistin:the controversical, adiponectin:the promising, and more to come[J]. Best Pract Res Clin Endocrinol Metab, 2005, 19(4):525-546.
[17] HUANG B, YUAN H D, KIM D Y, et al. Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferator-activated receptor-γ (PPARγ) and AMP-activated protein kinase (AMPK) pathways[J]. J Agric Food Chem, 2011, 59(8):3666-3673.
[18] 李慧玲, 吴骁, 王丹, 等. 木犀草苷对3T3-L1前脂肪细胞分化的抑制作用[J]. 中国医药导报, 2017, 14(2):16-19.
[19] JANG B C. Artesunate inhibits adipogeneis in 3T3-L1 preadipocytes by reducing the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3[J]. Biochem Biophys Res Commun, 2016, 474(1):220-225.
[20] PARK Y K, OBIANG-OBOUNOU B W, LEE J, et al. Anti-adipogenic effects on 3T3-L1 cells and zebrafish by tanshinone ⅡA[J]. Int J Mol Sci, 2017, 18(10):E2065.
[21] 赵丹, 王艳艳, 梁雄杰, 等. 淫羊藿苷对3T3-L1前脂肪细胞增殖及分化的影响[J]. 现代中西医结合杂志, 2017, 26(22):2398-2400, 2404.
[22] LI H, YUAN Y F, ZHANG Y L, et al. Icariin inhibits AMPK-dependent autophagy and adipogenesis in adipocytes in vitro and in a model of Graves' orbitopathy in vivo[J]. Front Physiol, 2017, 8:45.
[23] CHE Y Y, WANG Q H, XIAO R Y, et al. Kudinoside-D, a triterpenoid saponin derived from Ilex Kudingcha suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes[J]. Fitoterapia, 2018, 125:208-216.
[24] JANG M K, YUN Y R, KIM J H, et al. Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity[J]. Sci Rep, 2017, 7:40345.
[25] LIU X N, WANG S F, WU Z S, et al. Deoxyschizandrin loaded liposomes on the suppression lipid accumulation in 3T3-L1 adipocytes[J]. Molecules, 2018, 23(9):E2158.
[26] 栗茜, 彭莎, 候宁, 等. 穿心莲内酯通过下调PPARγ-C/EBPα抑制脂滴形成[J]. 天津中医药, 2018, 35(6):454-459.
[27] ZHANG T, ZHAO Q, XIAO X R, et al. Modulation of lipid metabolism by celastrol[J]. J Proteome Res, 2019, 18(3):1133-1144.
[28] LIU H M, LIU M H, JIN Z B, et al. Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway[J]. Food Funct, 2019, 10(6):3603-3614.
[29] HAO M J, LI Y, LIU L X, et al. The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes[J]. Bioorg Med Chem, 2017, 25(20):5506-5512.
[30] LIANG Y C, HU J C, LI P Y, et al. Torenia concolor Lindley var. formosana Yamazaki extracts improve inflammatory response and lipid accumulation via PPARs activation[J]. Biomedicine (Taipei), 2017, 7(3):18.
[31] 李吉萍, 张文友, 孙婷婷, 等. 板蓝根水提物对3T3-L1前脂肪细胞增殖和分化的影响[J]. 中国药理学通报, 2017, 33(8):1159-1164.
[32] 刘新迎, 王培训. 黄芪提取物对3T3-L1细胞的影响及其部分作用机制[J]. 现代中医药, 2018, 38(1):86-88, 102.
[33] 李慧玲, 刘天竹, 王丹, 等. 豆茶决明冲剂含药血清对3T3-L1前脂肪细胞分化的抑制作用[J]. 中药药理与临床, 2018, 34(1):89-92.
[34] ZHANG X H, WANG Z Q, KANG B G, et al. Antiobesity effect of Astilbe chinensis franch. Et savet. Extract through regulation of adipogenesis and AMP-activated protein kinase pathways in 3T3-L1 adipocyte and high-fat diet-induced C57BL/6N obese mice[J]. Evid Based Complement Alternat Med, 2018, 2018:1347612.
[35] MA L, HUANG L, PEI H Y, et al. Pharmacological effects of the water fraction of key components in the traditional Chinese prescription Mai Tong Fang on 3T3-L1 adipocytes and ob/ob diabetic mice[J]. Molecules, 2014, 19(9):14687-14698.
[36] YANG Z Z, WANG L L, ZHANG F, et al. Evaluating the antidiabetic effects of Chinese herbal medicine:Xiao-Ke-An in 3T3-L1 cells and KKAy mice using both conventional and holistic omics approaches[J]. BMC Complement Altern Med, 2015, 15:272.
[37] LEE H, SHIM E H, LEE M S, et al. Traditional medicine, Sobokchukeo-Tang, modulates the inflammatory response in adipocytes and macrophages[J]. Mol Med Rep, 2017, 15(1):117-124.
[38] PAN Y Y, ZHAO D D, YU N, et al. Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes[J]. R Soc Open Sci, 2017, 4(11):170917.
[39] LI X W, HUANG M X, LO K, et al. Anti-diabetic effect of a shihunine-rich extract of Dendrobiumloddigesii on 3T3-L1 cells and db/db mice by up-regulating AMPK-GLUT4-PPARα[J]. Molecules, 2019, 24(14):E2673.
[40] LIU Z H, XU L T, XU X Q, et al. Effects and mechanisms of iridoid glycosides from Patrinia scabiosaefolia on improving insulin resistance in 3T3-L1 adipocytes[J]. Food Chem Toxicol, 2019, 134:110806.
[41] ANUSREE S S, SINDHU G, PREETHA RANI M R, et al. Insulin resistance in 3T3-L1 adipocytes by TNF-α is improved by punicic acid through upregulation of insulin signalling pathway and endocrine function, and downregulation of proinflammatory cytokines[J]. Biochimie, 2018, 146:79-86.
[42] XU X Q, SAADELDEEN F S A, XU L T, et al. The mechanism of phillyrin from the leaves of Forsythia suspensa for improving insulin resistance[J]. Biomed Res Int, 2019, 2019:3176483.
[43] SHEN S N, LIAO Q W, ZHANG T, et al. Myricanol modulates skeletal muscle-adipose tissue crosstalk to alleviate high-fat diet-induced obesity and insulin resistance[J]. Br J Pharmacol, 2019, 176(20):3983-4001.
[44] 蔡红蝶, 宿树兰, 郭盛, 等. 黄蜀葵花中黄酮类成分对前脂肪细胞增殖、分化及胰岛素抵抗的影响[J]. 中国中药杂志, 2016, 41(24):4635-4641.
[45] ZHANG R X, QIN X Z, ZHANG T, et al. Astragalus polysaccharide improves insulin sensitivity via AMPK activation in 3T3-L1 adipocytes[J]. Molecules, 2018, 23(10):E2711.
[46] LI J P, YUAN Y, ZHANG W Y, et al. Effect of Radix isatidis polysaccharide on alleviating insulin resistance in type 2 diabetes mellitus cells and rats[J]. J Pharm Pharmacol, 2019, 71(2):220-229.
[47] 武晓丹, 刘欢, 周晶, 等. 三黄消渴汤对胰岛素抵抗3T3-L1脂肪细胞的影响[J]. 时珍国医国药, 2015, 26(3):560-562.
[48] 罗新新, 朱水兰, 李冰涛, 等. 葛根芩连汤激活PPARγ上调脂联素和GLUT4表达改善脂肪胰岛素抵抗[J]. 中国中药杂志, 2017, 42(23):4641-4648.
[49] YUAN L, TANG P, LI H J, et al. Serum from Jiao-Tai-Wan treated rats increases glucose consumption by 3T3-L1 adipocytes through AMPK pathway signaling[J]. Biosci Rep, 2019, 39(4):BSR20181286.
[50] SUOLANG P C, LIU B Q, CHEN J, et al. Protective effect and mechanism of Qiwei Tiexie capsule on 3T3-L1 adipocytes cells and rats with nonalcoholic fatty liver disease by regulating LXRα, PPARγ, and NF-κB-iNOS-NO signaling pathways[J]. J Ethnopharmacol, 2019, 236:316-325.
[51] CHAWLA A, LAZAR M A. Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival[J]. Proc Natl Acad Sci U S A, 1994, 91(5):1786-1790.
[52] ROSEN E D, HSU C H, WANG X Z, et al. C/EBPalpha induces adipogenesis through PPARgamma:a unified pathway[J]. Genes Dev, 2002, 16(1):22-26.
[53] ROSEN E D, SARRAF P, TROY A E, et al. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro[J]. Mol Cell, 1999, 4(4):611-617.
[54] WRIGHT H M, CLISH C B, MIKAMI T, et al. A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation[J]. J Biol Chem, 2000, 275(3):1873-1877.
[55] CAMP H S, CHAUDHRY A, LEFF T. A novel potent antagonist of peroxisome proliferator-activated receptor γ blocks adipocyte differentiation but does not revert the phenotype of terminally differentiated adipocytes[J]. Endocrinology, 2001, 142(7):3207-3213.