EGCG对高脂饮食GK大鼠白色脂肪米色化的诱导作用与机制研究

万丽玮, 曾鸿哲, 彭丽媛, 文帅, 刘昌伟, 鲍肃都, 安勤, 黄建安, 刘仲华

茶叶科学 ›› 2024, Vol. 44 ›› Issue (1) : 119-132.

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茶叶科学 ›› 2024, Vol. 44 ›› Issue (1) : 119-132. DOI: 10.13305/j.cnki.jts.2024.01.008
研究报告

EGCG对高脂饮食GK大鼠白色脂肪米色化的诱导作用与机制研究

  • 万丽玮, 曾鸿哲, 彭丽媛, 文帅, 刘昌伟, 鲍肃都, 安勤, 黄建安*, 刘仲华*
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Inductive Effect and Mechanism of EGCG on Beiging of White Adipose Tissue in High-fat Diet-fed GK Rats

  • WAN Liwei, ZENG Hongzhe, PENG Liyuan, WEN Shuai, LIU Changwei, BAO Sudu, AN Qin, HUANG Jian'an*, LIU Zhonghua*
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摘要

脂肪组织类型与人体代谢密切相关,通过饮食或营养干预将白色脂肪细胞转变为产热的米色脂肪细胞是一种减少脂肪积蓄、调节代谢的安全策略。目前关于白色脂肪组织米色化作用的研究多聚焦于肥胖群体,为探究EGCG对非肥胖代谢紊乱群体的内脏白色脂肪组织米色化的诱导作用及相关机制,采用非肥胖型自发性2型糖尿病模型Goto-Kakizaki(GK)大鼠,给予每日高脂饮食,并进行40 mg·kg-1和80 mg·kg-1 EGCG灌胃干预,检测GK大鼠的体质量、摄食量、脂肪组织细胞形态及米色化相关基因表达水平、UCP1蛋白表达水平,并进行转录组测序。结果表明,80 mg·kg-1 EGCG灌胃干预对GK大鼠摄食量和体质量无明显影响,但能够促使脂肪细胞呈现向多房型脂肪细胞转变趋势,并显著上调米色化相关的PpargPpargc1aUcp1基因表达水平和UCP1蛋白表达水平,具有诱导高脂饮食GK大鼠内脏附睾白色脂肪组织米色化的作用,且表现出调节脂质代谢的潜力。结合转录组分析结果表明,EGCG对高脂饮食GK大鼠白色脂肪组织米色化的诱导作用机制可能与PPAR信号通路、PI3K/Akt信号通路和MAPK信号通路有关。

Abstract

The types of adipose tissue are closely related to human metabolism. Transforming white adipocytes into thermogenic beige adipocytes through dietary or nutritional interventions is a safe strategy to reduce fat accumulation and regulate metabolism. Currently, research on the role of white adipose tissue beiging has mainly focused on obese populations. To explore the effect of EGCG on promoting the beiging of white adipose tissue in non-obese individuals with metabolic disorders and its related mechanisms, this study used non-obese, spontaneously diabetic type 2 GK rats. These rats were fed a high-fat diet and received 40 mg·kg-1 and 80 mg·kg-1 EGCG daily by gavage. In this study, we assessed body weight, food intake, cellular morphology of adipose tissue, gene expression levels associated with beiging, and protein expression levels of UCP1 in GK rats. Additionally, transcriptome sequencing was also performed on epididymal white adipose tissue. The results show that gavage intervention with 80 mg·kg-1 EGCG has no significant effect on the food intake and body weight of GK rats. It induced a trend of beiging in adipocytes towards a multilocular phenotype transformation, characterized by a decrease in cell size and an increase in cell number. Moreover, it significantly upregulated the expression levels of beiging-related genes Pparg, Ppargc1a, Ucp1 and the protein expression level of UCP1.This demonstrates the inducing effect of EGCG on the beiging of visceral epididymal white adipose tissue in high-fat diet-fed GK rats, indicating its potential in the regulation of lipid metabolism. Combined with transcriptome analysis, the results suggest that the induction mechanism of EGCG on the beiging of white adipose tissue in high-fat diet-fed GK rats may be associated with the PPAR signaling pathway, PI3K/Akt, and MAPK signaling pathway.

关键词

EGCG / GK大鼠 / 白色脂肪组织 / 非肥胖型 / 米色化

Key words

beiging / EGCG / Goto-Kakizaki rats / non-obesetype / white adipose tissue

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万丽玮, 曾鸿哲, 彭丽媛, 文帅, 刘昌伟, 鲍肃都, 安勤, 黄建安, 刘仲华. EGCG对高脂饮食GK大鼠白色脂肪米色化的诱导作用与机制研究[J]. 茶叶科学. 2024, 44(1): 119-132 https://doi.org/10.13305/j.cnki.jts.2024.01.008
WAN Liwei, ZENG Hongzhe, PENG Liyuan, WEN Shuai, LIU Changwei, BAO Sudu, AN Qin, HUANG Jian'an, LIU Zhonghua. Inductive Effect and Mechanism of EGCG on Beiging of White Adipose Tissue in High-fat Diet-fed GK Rats[J]. Journal of Tea Science. 2024, 44(1): 119-132 https://doi.org/10.13305/j.cnki.jts.2024.01.008
中图分类号: S571.1    R972+.6   

参考文献

[1] Camp H S, Ren D, Leff T.Adipogenesis and fat-cell function in obesity and diabetes[J]. Trends in Molecular Medicine, 2002, 8(9): 442-447.
[2] Sakers A, De Siqueira M K, Seale P, et al. Adipose-tissue plasticity in health and disease[J]. Cell, 2022, 185(3): 419-446.
[3] Lee Y H, Mottillo E P, Granneman J G.Adipose tissue plasticity from WAT to BAT and in between[J]. Biochimica et Biophysica Acta, 2014, 1842(3): 358-369.
[4] Ma Y R, Shen S Y, Yan Y, et al.Adipocyte thyroid hormone β receptor-mediated hormone action fine-tunes intracellular glucose and lipid metabolism and systemic homeostasis[J]. Diabetes, 2023, 72(5): 562-574.
[5] Yang N F, Wang Y X, Tian Q, et al.Blockage of PPARγ T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions[J]. Cell Death & Differentiation, 2023, 30(3): 766-778.
[6] Wang Q, Li H X, Tajima K, et al.Post-translational control of beige fat biogenesis by PRDM16 stabilization[J]. Nature, 2022, 609(7925): 151-158.
[7] Jia M, Xu T C, Xu Y J, et al.Dietary fatty acids activate or deactivate brown and beige fat[J]. Life Sciences, 2023, 330: 121978. doi: 10.1016/j.lfs.2023.121978.
[8] Cui C J, Jin J L, Guo L N, et al.Beneficial impact of epigallocatechingallate on LDL-C through PCSK9/LDLR pathway by blocking HNF1α and activating FoxO3a[J]. Journal of Translational Medicine, 2020, 18(1): 195. doi: 10.1186/s12967-020-02362-4.
[9] Lambert J D, Sang S M, Yang C S.Biotransformation of green tea polyphenols and the biological activities of those metabolites[J]. Molecular Pharmaceutics, 2007, 4(6): 819-825. doi: 10.1021/mp700075m.
[10] Lee M S, Kim Y.(-)-Epigallocatechin-3-gallate enhances uncoupling protein 2 gene expression in 3T3-L1 adipocytes[J]. Bioscience, Biotechnology, and Biochemistry, 2009, 73(2): 434-436.
[11] Lee M S, Shin Y, Jung S, et al.Effects of epigallocatechin-3-gallate on thermogenesis and mitochondrial biogenesis in brown adipose tissues of diet-induced obese mice[J]. Food & Nutrition Research, 2017, 61(1) : 1325307. doi: 10.1080/16546628.2017.1325307.
[12] Mi Y, Liu X, Tian H, et al.EGCG stimulates the recruitment of brite adipocytes, suppresses adipogenesis and counteracts TNF-α-triggered insulin resistance in adipocytes[J]. Food & Function, 2018, 9(6): 3374-3386.
[13] Nahmgoong H, Jeon Y G, Park E S, et al.Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics[J]. Cell Metabolism, 2022, 34(3): 458-472.
[14] Li F, Gao C, Yan P, et al.EGCG reduces obesity and white adipose tissue gain partly through AMPK activation in mice[J]. Front Pharmacol, 2018, 9: 1366. doi: 10.3389/fphar.2018.01366.
[15] Argoud K, Wilder S P, Mcateer M A, et al.Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto-Kakizaki rats[J]. Diabetologia, 2006, 49(11): 2679-2688.
[16] Szkudelska K, Okulicz M, Hertig I, et al.Resveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats[J]. Biomedicine & Pharmacotherapy, 2020, 125: 110026. doi: 10.1016/j.biopha.2020.110026.
[17] Brunham L R.HDL as a causal factor in atherosclerosis: insights from human genetics[J]. Current Atherosclerosis Reports, 2016, 18(12): 71. doi: 10.1007/s11883-016-0623-0.
[18] Matafome P, Louro T, Rodrigues L, et al.Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia[J]. Diabetes Metabolism Research and Reviews, 2011, 27(1): 54-62.
[19] Kiya M, Tamura Y, Takeno K, et al.Adipose insulin resistance and decreased adiponectin are correlated with metabolic abnormalities in nonobese men[J]. The Journal of Clinical Endocrinology & Metabolism, 2021, 106(5): e2228-e2238.
[20] Yang C S, Hong J.Prevention of chronic diseases by tea: possible mechanisms and human relevance[J]. Annual Review of Nutrition, 2013, 33: 161-81.
[21] Nair A B, Jacob S.A simple practice guide for dose conversion between animals and human[J]. Journal of Basic and Clinical Pharmacy, 2016, 7(2): 27-31.
[22] Grove K A, Sae-Tan S, Kennett M J, et al.(-)-Epigallocatechin-3-gallate inhibits pancreatic lipase and reduces body weight gain in high fat-fed obese mice[J]. Obesity, 2012, 20(11): 2311-2313.
[23] Uchiyama Y, Suzuki T, Mochizuki K, et al.Dietary supplementation with (-)-epigallocatechin-3-gallate reduces inflammatory response in adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats[J]. Journal of Agricultural and Food Chemistry, 2013, 61(47): 11410-11417.
[24] Jeon Y G, Kim Y Y, Lee G, et al.Physiological and pathological roles of lipogenesis[J]. Nature Metabolism, 2023, 5(5): 735-759.
[25] Wang B, Du M.Increasing adipocyte number and reducing adipocyte size: the role of retinoids in adipose tissue development and metabolism[J]. Critical Reviews in Food Science and Nutrition, 2023: 1-18. doi: 10.1080/10408398.2023.2227258.
[26] Inagaki T, Sakai J, Kajimura S.Transcriptional and epigenetic control of brown and beige adipose cell fate and function[J]. Nature Reviews Molecular Cell Biology, 2016, 17(8): 480-495.
[27] Keinan O, Valentine J M, Xiao H, et al.Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes[J]. Nature, 2021, 599(7884): 296-301.
[28] Kajimura S, Spiegelman B M, Seale P.Brown and beige fat: physiological roles beyond heat generation[J]. Cell Metabolism, 2015, 22(4): 546-559.
[29] Ikeda K, Kang Q, Yoneshiro T, et al.UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis[J]. Nature Medicine, 2017, 23(12): 1454-1465.
[30] Hong F, Pan S J, Guo Y, et al.PPARs as nuclear receptors for nutrient and energy metabolism[J]. Molecules, 2019, 24(14): 2545. doi: 10.3390/molecules24142545.
[31] Göransson O, Kopietz F, Rider M H.Metabolic control by AMPK in white adipose tissue[J]. Trends in Endocrinology & Metabolism, 2023, 34(11): 704-717.
[32] Wu L Y, Zhang L N, Li B H, et al.AMP-activated protein kinase (AMPK) regulates energy metabolism through modulating thermogenesis in adipose tissue[J]. Frontiers in Physiology, 2018, 9: 122. doi: 10.3389/fphys.2018.00122.
[33] Srinivasan K, Ramarao P.Animal models in type 2 diabetes research: an overview[J]. Indian Journal of Medical Research, 2007, 125(3): 451-472.
[34] Hou J, Li Z, Zhong W, et al.Temporal transcriptomic and proteomic landscapes of deteriorating pancreatic islets in type 2 diabetic rats[J]. Diabetes, 2017, 66(8): 2188-2200.
[35] 雷蕾, 林智立, 王琳琳, 等. 2型糖尿病发病过程中胰岛炎症的动力学机理[J]. 科学通报, 2020, 65(35): 4139-4148.
Lei L, Lin Z L, Wang L L, et al.The dynamics mechanism of islet inflammation during type 2 diabetes progress[J]. Chinese Science Bulletin, 2020, 65: 4139-4148.
[36] Cai E P, Lin J K.Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic β cells[J]. Journal of Agricultural and Food Chemistry, 2009, 57(20): 9817-9827.
[37] Ortsäter H, Grankvist N, Wolfram S, et al.Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice[J]. Nutrition & Metabolism, 2012, 9: 11. doi: 10.1186/1743-7075-9-11.
[38] Kobayashi N, Ueki K, Okazaki Y, et al.Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance[J]. PNAS, 2011, 108(14): 5753-5758.
[39] Araiz C, Yan A, Bettedi L, et al.Enhanced β-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110α inactivation in adipose tissue[J]. Nature Communications, 2019, 10(1): 1546. doi: 10.1038/s41467-019-09514-1.
[40] Hwang I, Kim J B.Two faces of white adipose tissue with heterogeneous adipogenic progenitors[J]. Diabetes & Metabolism Journal, 2019, 43(6): 752-762.
[41] Tian X, Xie G, Xiao H, et al.CXCR4 knockdown prevents inflammatory cytokine expression in macrophages by suppressing activation of MAPK and NF-κB signaling pathways[J]. Cell & Bioscience, 2019, 9: 55. doi: 10.1186/s13578-019-0315-x.
[42] Okla M, Kim J, Koehler K, et al.Dietary factors promoting brown and beige fat development and thermogenesis[J]. Advances in Nutrition, 2017, 8(3): 473-483.
[43] Wang W S, Seale P.Control of brown and beige fat development[J]. Nature Reviews Molecular Cell Biology, 2016, 17(11): 691-702.
[44] Finlin B S, Memetimin H, Confides A L, et al.Human adipose beiging in response to cold and mirabegron[J]. JCI Insight, 2018, 3(15): e121510. doi: 10.1172/jci.insight.121510.
[45] Whittle A J, Jiang M, Peirce V, et al.Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans[J]. Nature Communications, 2015, 6: 8951. doi: 10.1038/ncomms9951.
[46] Laeger T, Baumeier C, Wilhelmi I, et al.FGF21 improves glucose homeostasis in an obese diabetes-prone mouse model independent of body fat changes[J]. Diabetologia, 2017, 60(11): 2274-2284.
[47] Zhang Y, Xie C, Wang H, et al.Irisin exerts dual effects on browning and adipogenesis of human white adipocytes[J]. American Journal of Physiology-Endocrinology and Metabolism, 2016, 311(2): E530-E541. doi: 10.1152/ajpendo.00094.2016.

基金

国家茶叶产业技术体系(CARS-19)、茶叶功能成分优异资源高效利用技术研究(湘财农指[2021]0015号)

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