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

Journal of Tea Science ›› 2024, Vol. 44 ›› Issue (1) : 119-132.

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Journal of Tea Science ›› 2024, Vol. 44 ›› Issue (1) : 119-132. DOI: 10.13305/j.cnki.jts.2024.01.008
Research Paper

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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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.

Key words

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

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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

References

[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.
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