表观遗传修饰对脂肪组织产热的调控进展

doi:10.16288/j.yczz.22-151

遗传 ›› 2022, Vol. 44 ›› Issue (10): 867-880.doi: 10.16288/j.yczz.22-151

表观遗传修饰对脂肪组织产热的调控进展

赵清雯¹(), 潘东宁²()

1. 浙江大学医学院附属杭州市第一人民医院老年医学科,杭州 310006
2. 复旦大学基础医学院代谢分子医学教育部重点实验室,上海 200032

收稿日期:2022-05-09 修回日期:2022-07-22 出版日期:2022-10-20 发布日期:2022-08-11
通讯作者: 潘东宁 E-mail:17111010048@fudan.edu.cn;dongning.pan@fudan.edu.cn
作者简介:赵清雯,博士,助理研究员,研究方向：棕色脂肪的代谢调控。E-mail: 17111010048@fudan.edu.cn
基金资助:
中国博士后科学基金(2020M680053);国家自然科学基金项目(31970710)

Progress on the epigenetic regulation of adipose tissue thermogenesis

Qingwen Zhao¹(), Dongning Pan²()

1. Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
2. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Fudan University, Shanghai 200032, China

Received:2022-05-09 Revised:2022-07-22 Online:2022-10-20 Published:2022-08-11
Contact: Pan Dongning E-mail:17111010048@fudan.edu.cn;dongning.pan@fudan.edu.cn
Supported by:
the Fellowship of China Postdoctoral Science Foundation(2020M680053);the National Natural Science Foundation of China(31970710)

摘要/Abstract

摘要：

棕色和米色脂肪组织的激活可以增加葡萄糖、脂肪酸等底物的消耗,调节全身的能量平衡,改善肥胖病、2型糖尿病等代谢性疾病。研究产热脂肪组织的调控机制,将为代谢性疾病的防治提供新策略。目前研究已表明,表观遗传修饰在脂肪组织的分化和产热等方面发挥重要的调控作用。本文从DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA等方面,对表观遗传修饰在脂肪组织的分化和产热等方面发挥的调控作用进行综述,为深入研究脂肪组织的激活提供新思路。

关键词: 表观遗传修饰, 棕色脂肪组织, 米色脂肪组织, 米色化, 产热

Abstract:

The activation of brown adipose tissues and beige adipose tissues can utilize more substrates, including glucose and fatty acids, regulate the energy balance of the whole body and improve metabolic diseases such as obesity and type Ⅱ diabetes. Elucidating the regulatory mechanisms underlying the thermogenic adipose program may provide excellent targets for therapeutics against metabolic diseases. The current studies have indicated that epigenetic modifications are vital for regulating differentiation and thermogenesis of adipose tissues. In this review, we summarize the recent progress of epigenetic modifications in adipose tissue development and thermogenesis from the aspects of DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs in order to provide new ideas for further studying the activation of adipose tissues.

Key words: epigenetic modifications, brown adipose tissues, beige adipose tissues, browning, thermogenesis

赵清雯, 潘东宁. 表观遗传修饰对脂肪组织产热的调控进展[J]. 遗传, 2022, 44(10): 867-880.

Qingwen Zhao, Dongning Pan. Progress on the epigenetic regulation of adipose tissue thermogenesis[J]. Hereditas(Beijing), 2022, 44(10): 867-880.

图/表 3

表1

图1

图2

参考文献 89

[1]	Smith KB, Smith MS. Obesity statistics. Prim Care, 2016, 43(1): 121-135. doi: 10.1016/j.pop.2015.10.001
[2]	Kitzinger H, Karle B. The epidemiology of obesity. Eur Surg, 2013, 45(2): 80-82. doi: 10.1007/s10353-013-0196-x
[3]	Kajimura S, Spiegelman BM, Seale P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab, 2015, 22(4): 546-559. doi: 10.1016/j.cmet.2015.09.007 pmid: 26445512
[4]	Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, Vetrivelan R, Lu GZ, Laznik- Bogoslavski D, Hasenfuss SC, Kajimura S, Gygi SP, Spiegelman BM. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell, 2015, 163(3): 643-655. doi: 10.1016/j.cell.2015.09.035 pmid: 26496606
[5]	Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K, Wang Q, Kim K, Shinoda K, Sponton CH, Brown Z, Brack A, Kajimura S. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature, 2019, 565(7738): 180-185. doi: 10.1038/s41586-018-0801-z
[6]	Ikeda K, Kang QQ, Yoneshiro T, Camporez JP, Maki H, Homma M, Shinoda K, Chen Y, Lu XD, Maretich P, Tajima K, Ajuwon KM, Soga T, Kajimura S. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat Med, 2017, 23(12): 1454-1465. doi: 10.1038/nm.4429 pmid: 29131158
[7]	Jung SM, Doxsey WG, Le J, Haley JA, Mazuecos L, Luciano AK, Li H, Jang C, Guertin DA. In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate. Cell Rep, 2021, 36(4): 109459. doi: 10.1016/j.celrep.2021.109459
[8]	Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med, 2009, 360(15): 1518-1525. doi: 10.1056/NEJMoa0808949
[9]	Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest, 2012, 123(1): 215-223.
[10]	Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, Saito M. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes (Lond), 2014, 38(6): 812-817. doi: 10.1038/ijo.2013.206
[11]	Berbée JF, Boon MR, Khedoe PSJ, Bartelt A, Schlein C, Worthmann A, Kooijman S, Hoeke G, Mol IM, John C, Jung C, Vazirpanah N, Brouwers LPJ, Gordts PLSM, Esko JD, Hiemstra PS, Havekes LM, Scheja L, Heeren J, Rensen PCN. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat Commun, 2015, 6: 6356. doi: 10.1038/ncomms7356 pmid: 25754609
[12]	Li FF, Jing J, Movahed M, Cui X, Cao Q, Wu R, Chen ZY, Yu LQ, Pan Y, Shi HD, Shi H, Xue BZ. Epigenetic interaction between UTX and DNMT1 regulates diet- induced myogenic remodeling in brown fat. Nat Commun, 2021, 12(1):6838. doi: 10.1038/s41467-021-27141-7
[13]	Li FF, Cui X, Jing J, Wang SR, Shi HD, Xue BZ, Shi H. Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice. Life(Basel), 2021, 11(12): 1325.
[14]	Wang SR, Cao Q, Cui X, Jing J, Li FF, Shi HD, Xue BZ, Shi H. Dnmt3b deficiency in Myf5⁺-brown fat precursor cells promotes obesity in female mice. Biomolecules, 2021, 11(8): 1087. doi: 10.3390/biom11081087
[15]	Yang QY, Liang XW, Sun XF, Zhang LP, Fu X, Rogers CJ, Berim A, Zhang SM, Wang SB, Wang B, Foretz M, Viollet B, Gang DR, Rodgers BD, Zhu MJ, Du M. AMPK/ α-ketoglutarate axis dynamically mediates DNA demethylation in the Prdm16 promoter and brown adipogenesis. Cell Metab, 2016, 24(4): 542-554. doi: 10.1016/j.cmet.2016.08.010
[16]	Shore A, Karamitri A, Kemp P, Speakman JR, Lomax MA. Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue. Diabetologia, 2010, 53(6): 1164-1173. doi: 10.1007/s00125-010-1701-4 pmid: 20238096
[17]	Damal Villivalam S, You D, Kim J, Lim HW, Xiao H, Zushin P-JH, Oguri Y, Amin P, Kang S. TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis. Nat Commun, 2020, 11(1): 313. doi: 10.1038/s41467-019-14125-x
[18]	Jin QH, Wang CC, Kuang XH, Feng XS, Sartorelli V, Ying H, Ge K, Dent SYR. Gcn5 and PCAF regulate PPAR γ and Prdm16 expression to facilitate brown adipogenesis. Mol Cell Biol, 2014, 34(19): 3746-3753. doi: 10.1128/MCB.00622-14
[19]	Kawabe Y, Mori J, Morimoto H, Yamaguchi M, Miyagaki S, Ota T, Tsuma Y, Fukuhara S, Nakajima H, Oudit GY, Hosoi H. ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue. Am J Physiol Endocrinol Metab, 2019, 317(6): E1140-E1149. doi: 10.1152/ajpendo.00311.2019
[20]	Lai BB, Lee J-E, Jang Y, Wang LF, Peng WQ, Ge K. MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis. Nucleic Acids Res, 2017, 45(11): 6388-6403. doi: 10.1093/nar/gkx234 pmid: 28398509
[21]	Li FF, Wu R, Cui X, Zha LQ, Yu L, Shi H, Xue BZ. Histone deacetylase1 (HDAC1) negatively regulates thermogenic program in brown adipocytes via coordinated regulation of histone H3 lysine 27 (H3K27) deacetylation and methylation. J Biol Chem, 2016, 291(9): 4523-4536. doi: 10.1074/jbc.M115.677930
[22]	Shinoda K, Ohyama K, Hasegawa Y, Chang H-Y, Ogura M, Sato A, Hong H, Hosono T, Sharp LZ, Scheel DW, Graham M, Ishihama Y, Kajimura S. Phosphoproteomics identifies CK2 as a negative regulator of beige adipocyte thermogenesis and energy expenditure. Cell Metab, 2015, 22(6): 997-1008. doi: 10.1016/j.cmet.2015.09.029 pmid: 26525534
[23]	Ferrari A, Longo R, Fiorino E, Silva R, Mitro N, Cermenati G, Gilardi F, Desvergne B, Andolfo A, Magagnotti C, Caruso D, De Fabiani E, Hiebert SW, Crestani M. HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning. Nat Commun, 2017, 8(1): 93. doi: 10.1038/s41467-017-00182-7 pmid: 28733645
[24]	Liao JL, Jiang J, Jun HJ, Qiao XN, Emont MP, Kim D-I, Wu J.HDAC3-selective inhibition activates brown and beige fat through PRDM16. Endocrinology, 2018, 159(7): 2520-2527. doi: 10.1210/en.2018-00257 pmid: 29757434
[25]	Emmett MJ, Lim H-W, Jager J, Richter HJ, Adlanmerini M, Peed LC, Briggs ER, Steger DJ, Ma T, Sims CA, Baur JA, Pei LM, Won K-J, Seale P, Gerhart-Hines Z, Lazar MA. Histone deacetylase3 prepares brown adipose tissue for acute thermogenic challenge. Nature, 2017, 546(7659): 544-548. doi: 10.1038/nature22819
[26]	Chatterjee TK, Basford JE, Knoll E, Tong WS, Blanco V, Blomkalns AL, Rudich S, Lentsch AB, Hui DY, Weintraub NL. HDAC9 knockout mice are protected from adipose tissue dysfunction and systemic metabolic disease during high-fat feeding. Diabetes, 2014, 63(1): 176-187. doi: 10.2337/db13-1148 pmid: 24101673
[27]	Mayoral R, Osborn O, Mcnelis J, Johnson AM, Izquierdo CL, Chung H, Li PP, Traves PG, Bandyopadhyay G, Pessentheiner AR, Ofrecio JM, Cook JR, Qiang L, Accili D, Olefsky JM. Adipocyte SIRT1 knockout promotes PPARγ activity, adipogenesis and insulin sensitivity in chronic-HFD and obesity. Mol Metab 2015, 4(5): 378-391. doi: 10.1016/j.molmet.2015.02.007 pmid: 25973386
[28]	Qiang L, Wang LH, Kon N, Zhao WH, Lee S, Zhang YY, Rosenbaum M, Zhao YM, Gu W, Farmer SR, Accili D. Brown remodeling of white adipose tissue by SirT1- dependent deacetylation of Pparγ. Cell, 2012, 150(3): 620-632. doi: 10.1016/j.cell.2012.06.027 pmid: 22863012
[29]	Zhou YF, Song TX, Peng J, Zhou Z, Wei HK, Zhou R, Jiang SW, Peng J. SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro. Oncotarget, 2016, 7(47): 77707-77720. doi: 10.18632/oncotarget.12774 pmid: 27776347
[30]	Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with PPARγ. Mol Biol Cell, 2009, 20(3): 801-808. doi: 10.1091/mbc.E08-06-0647 pmid: 19037106
[31]	Shuai L, Zhang L-N, Li B-H, Tang C-L, Wu L-Y, Li J, Li J-Y. SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue. Diabetes, 2019, 68(7): 1449-1461. doi: 10.2337/db18-1103 pmid: 31010955
[32]	Yao L, Cui XN, Chen Q, Yang XY, Fang FD, Zhang J, Liu GQ, Jin WZ, Chang YS. Cold-inducible SIRT6 regulates thermogenesis of brown and beige fat. Cell Rep, 2017, 20(3): 641-654. doi: S2211-1247(17)30900-2 pmid: 28723567
[33]	Chen Q, Hao WH, Xiao CY, Wang RH, Xu XL, Lu HY, Chen WP, Deng C-X. SIRT6 is essential for adipocyte differentiation by regulating mitotic clonal expansion. Cell Rep, 2017, 18(13): 3155-3166. doi: S2211-1247(17)30323-6 pmid: 28355567
[34]	Fang J, Ianni A, Smolka C, Vakhrusheva O, Nolte H, Krüger M, Wietelmann A, Simonet NG, Adrian-Segarra JM, Vaquero A, Braun T, Bober E. Sirt 7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1. Proc Natl Acad Sci USA, 2017, 114(40): E8352-E8361.
[35]	Jang Y, Broun A, Wang CC, Park Y-K, Zhuang LN, Lee J-E, Froimchuk E, Liu CY, Ge K. H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development. Nucleic Acids Res, 2019, 47(2): 607-620. doi: 10.1093/nar/gky982 pmid: 30335158
[36]	Lee J-E, Wang CC, Xu SLY, Cho Y-W, Wang LF, Feng XR, Baldridge A, Sartorelli V, Zhuang LN, Peng WQ, Ge K. H3K4 mono-and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. eLife, 2013, 2(1): e01503. doi: 10.7554/eLife.01503
[37]	Lee J, Saha PK, Yang Q-H, Lee S, Park JY, Suh Y, Lee S-K, Chan L, Roeder RG, Lee JW. Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc Natl Acad Sci USA, 2008, 105(49): 19229-19234. doi: 10.1073/pnas.0810100105
[38]	Ohno H, Shinoda K, Ohyama K, Sharp LZ, Kajimura S. EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature, 2013, 504(7478): 163-167. doi: 10.1038/nature12652
[39]	Wang LF, Xu SLY, Lee JE, Baldridge A, Grullon S, Peng WQ, Ge K. Histone H3K9 methyltransferase G9a represses PPARγ expression and adipogenesis. EMBO J, 2013, 32(1): 45-59. doi: 10.1038/emboj.2012.306 pmid: 23178591
[40]	Liu Y, Maekawa T, Yoshida K, Muratani M, Chatton B, Ishii S. The transcription factor ATF7 controls adipocyte differentiation and thermogenic gene programming. iScience, 2019, 13(3): 98-112. doi: 10.1016/j.isci.2019.02.013
[41]	Wang LF, Jin QH, Lee J-E, Su I-H, Ge K. Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate adipogenesis. Proc Natl Acad Sci USA, 2010, 107(16): 7317-7322. doi: 10.1073/pnas.1000031107
[42]	Wu XH, Li JQ, Chang KX, Yang F, Jia Z, Sun C, Li Q, Xu YQ. Histone H3 methyltransferase Ezh2 promotes white adipocytes but inhibits brown and beige adipocyte differentiation in mice. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866(6): 158901.
[43]	Zhuang LN, Jang Y, Park Y-K, Lee J-E, Jain S, Froimchuk E, Broun A, Liu CY, Gavrilova O, Ge K. Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function. Nat Commun, 2018, 9(1): 1796. doi: 10.1038/s41467-018-04127-6 pmid: 29728617
[44]	Zhao QW, Zhang Z, Rong WQ, Jin WW, Yan LU, Jin WF, Xu YJ, Cui X, Tang Q-Q, Pan DN. KMT5c modulates adipocyte thermogenesis by regulating Trp53 expression. Proc Natl Acad Sci USA, 2020, 117(36): 22413-22422. doi: 10.1073/pnas.1922548117
[45]	Pedrotti S, Caccia R, Neguembor MV, Garcia-Manteiga JM, Ferri G, De Palma C, Canu T, Giovarelli M, Marra P, Fiocchi A, Molineris I, Raso M, Sanvito F, Doglioni C, Esposito A, Clementi E, Gabellini D. The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli. Sci Adv, 2019, 5(4): eaav1472. doi: 10.1126/sciadv.aav1472
[46]	Zeng X, Jedrychowski MP, Chen Y, Serag S, Lavery GG, Gygi SP, Spiegelman BM. Lysine-specific demethylase1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation. Genes Dev, 2016, 30(16): 1822-36. doi: 10.1101/gad.285312.116
[47]	Duteil D, Metzger E, Willmann D, Karagianni P, Friedrichs N, Greschik H, Günther T, Buettner R, Talianidis I, Metzger D, Schüle R. LSD1 promotes oxidative metabolism of white adipose tissue. Nat Commun, 2014, 5(1): 4093. doi: 10.1038/ncomms5093
[48]	Duteil D, Tosic M, Willmann D, Georgiadi A, Kanouni T, Schüle R. Lsd1 prevents age-programed loss of beige adipocytes. Proc Natl Acad Sci USA, 2017, 114(20): 5265-5270. doi: 10.1073/pnas.1702641114
[49]	Duteil D, Tosic M, Lausecker F, Nenseth HZ, Müller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L, Manke T, Kornfeld JW, Brüning JC, Zagoriy V, Meret M, Dengjel J, Kanouni T, Schüle R. Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue. Cell Rep, 2016, 17(4): 1008-1021. doi: S2211-1247(16)31292-X pmid: 27760309
[50]	Abe Y, Rozqie R, Matsumura Y, Kawamura T, Nakaki R, Tsurutani Y, Tanimura-Inagaki K, Shiono A, Magoori K, Nakamura K, Ogi S, Kajimura S, Kimura H, Tanaka T, Fukami K, Osborne TF, Kodama T, Aburatani H, Inagaki T, Sakai J. JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis. Nat Commun, 2015, 6(1): 7052. doi: 10.1038/ncomms8052
[51]	Abe Y, Fujiwara Y, Takahashi H, Matsumura Y, Sawada T, Jiang S, Nakaki R, Uchida A, Nagao N, Naito M, Kajimura S, Kimura H, Osborne TF, Aburatani H, Kodama T, Inagaki T, Sakai J. Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. Nat Commun, 2018, 9(1): 1-16. doi: 10.1038/s41467-017-02088-w
[52]	Zha L, Li FF, Wu R, Artinian L, Rehder V, Yu LQ, Liang HJ, Xue BZ, Shi H. The histone demethylase UTX promotes brown adipocyte thermogenic program via coordinated regulation of H3K27 demethylation and acetylation. J Biol Chem, 2015, 290(41): 25151-25163. doi: 10.1074/jbc.M115.662650 pmid: 26306033
[53]	Pan DN, Huang L, Zhu LJ, Zou T, Ou JH, Zhou W, Wang Y-X. Jmjd3-mediated H3K27me3 dynamics orchestrate brown fat development and regulate white fat plasticity. Dev Cell, 2015, 35(5): 568-583. doi: S1534-5807(15)00716-9 pmid: 26625958
[54]	Huang X, Chen YQ, Xu GL, Peng SH. DNA methylation in adipose tissue and the development of diabetes and obesity. Hereditas (Beijing), 2018, 41(2):98-110.
	黄鑫, 陈永强, 徐国良, 彭淑红. 脂肪组织 DNA 甲基化与糖尿病和肥胖的发生发展. 遗传, 2018, 41(2): 98-110.
[55]	Wu LY, Xia MF, Duan YN, Zhang LN, Jiang HW, Hu XB, Yan HM, Zhang YQ, Gu YS, Shi HC, Li J, Gao X, Li JY. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans. Cell Death Dis, 2019, 10(6): 468. doi: 10.1038/s41419-019-1706-y pmid: 31197160
[56]	Zhou YF, Peng J, Jiang SW. Role of histone acetyltransferases and histone deacetylases in adipocyte differentiation and adipogenesis. Eur J Cell Biol, 2014, 93(4): 170-177. doi: 10.1016/j.ejcb.2014.03.001 pmid: 24810880
[57]	Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet, 2016, 17(8): 487-500. doi: 10.1038/nrg.2016.59 pmid: 27346641
[58]	Trisciuoglio D, Di Martile M, Del Bufalo D. Emerging role of histone acetyltransferase in stem cells and cancer. Stem Cells Int, 2018, 2018(2): 8908751.
[59]	Jin QH, Yu LR, Wang LF, Zhang ZJ, Kasper LH, Lee JE, Wang CC, Brindle PK, Dent SYR, Ge K. Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J, 2011, 30(2): 249-262. doi: 10.1038/emboj.2010.318 pmid: 21131905
[60]	Ong BX, Brunmeir R, Zhang QY, Peng X, Idris M, Liu CG, Xu F. Regulation of thermogenic adipocyte differentiation and adaptive thermogenesis through histone acetylation. Front Endocrinol (Lausanne), 2020, 2020(11): 95.
[61]	Galmozzi A, Mitro N, Ferrari A, Gers E, Gilardi F, Godio C, Cermenati G, Gualerzi A, Donetti E, Rotili D, Valente S, Guerrini U, Caruso D, Mai A, Saez E, De Fabiani E, Crestani M. Inhibition of class I histone deacetylases unveils a mitochondrial signature and enhances oxidative metabolism in skeletal muscle and adipose tissue. Diabetes, 2013, 62(3): 732-742. doi: 10.2337/db12-0548 pmid: 23069623
[62]	Finkel T, Deng C-X, Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature, 2009, 460(7255): 587-591. doi: 10.1038/nature08197
[63]	Shi T, Wang F, Stieren E, Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem, 2005, 280(14): 13560-13567. doi: 10.1074/jbc.M414670200 pmid: 15653680
[64]	Porter LC, Franczyk MP, Pietka T, Yamaguchi S, Lin JB, Sasaki Y, Verdin E, Apte RS, Yoshino J. NAD⁺-dependent deacetylase SIRT3 in adipocytes is dispensable for maintaining normal adipose tissue mitochondrial function and whole body metabolism. Am J Physiol Endocrinol Metab, 2018, 315(4): E520-E530. doi: 10.1152/ajpendo.00057.2018
[65]	Hong JY, Li SJ, Wang XY, Mei CG, Zan LS. Study of expression analysis of SIRT4 and the coordinate regulation of bovine adipocyte differentiation by SIRT4 and its transcription factors. Biosci Rep, 2018, 38(6): BSR20181705.
[66]	Zhao ZB, Shilatifard A. Epigenetic modifications of histones in cancer. Genome Biol, 2019, 20(1): 245. doi: 10.1186/s13059-019-1870-5 pmid: 31747960
[67]	Hyun K, Jeon J, Park K, Kim J. Writing, erasing and reading histone lysine methylations. Exp Mol Med, 2017, 49(4): e324. doi: 10.1038/emm.2017.11
[68]	Peng X, Zhang QY, Liao C, Han WP, Xu F. Epigenomic control of thermogenic adipocyte differentiation and function. Int J Mol Sci, 2018, 19(6): 1793. doi: 10.3390/ijms19061793
[69]	Wang CC, Lee J-E, Lai BB, Macfarlan TS, Xu SLY, Zhuang LN, Liu CY, Peng WQ, Ge K. Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition. Proc Natl Acad Sci USA, 2016, 113(42): 11871-11876. doi: 10.1073/pnas.1606857113
[70]	Sambeat A, Gulyaeva O, Dempersmier J, Tharp KM, Stahl A, Paul SM, Sul HS. LSD1 interacts with Zfp516 to promote UCP1 transcription and brown fat program. Cell Rep, 2016, 15(11): 2536-2549. doi: 10.1016/j.celrep.2016.05.019 pmid: 27264172
[71]	Lin JZ, Farmer SR. LSD1—a pivotal epigenetic regulator of brown and beige fat differentiation and homeostasis. Genes Dev, 2016, 30(16): 1793-1795. doi: 10.1101/gad.288720.116
[72]	Liu WH, Ji YQ, Zhang BN, Chu HP, Yin CY, Xiao YF. Stat5a promotes brown adipocyte differentiation and thermogenic program through binding and transactivating the Kdm6a promoter. Cell Cycle, 2020, 19(8): 895-905. doi: 10.1080/15384101.2020.1731644 pmid: 32207362
[73]	Shapira SN, Lim H-W, Rajakumari S, Sakers AP, Ishibashi J, Harms MJ, Won K-J, Seale P. EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex. Genes Dev, 2017, 31(7): 660-673. doi: 10.1101/gad.294405.116
[74]	Liu TY, Mi L, Xiong J, Orchard P, Yu Q, Yu L, Zhao X-Y, Meng Z-X, Parker SCJ, Lin JD, Li SM. BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning. Nat Commun, 2020, 11(1): 2379. doi: 10.1038/s41467-020-16148-1 pmid: 32404872
[75]	Guo YT, Miao XY. MicroRNAs in the regulation of brown adipocyte differentiation. Hereditas (Beijing), 2015, 37(3): 240-249.
	郭云涛, 苗向阳. 调控褐色脂肪细胞分化的microRNAs. 遗传, 2015, 37(3): 240-249.
[76]	Trajkovski M, Ahmed K, Esau CC, Stoffel M.MyomiR-133 regulates brown fat differentiation through Prdm16. Nat Cell Biol, 2012, 14(12): 1330-1335. pmid: 23143398
[77]	Sun L, Trajkovski M. MiR-27 orchestrates the transcriptional regulation of brown adipogenesis. Metabolism, 2014, 63(2): 272-282. doi: 10.1016/j.metabol.2013.10.004
[78]	Chou C-F, Lin Y-Y, Wang H-K, Zhu XL, Giovarelli M, Briata P, Gherzi R, Garvey WT, Chen C-Y. KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression. Diabetes, 2014, 63(9): 2949-2961. doi: 10.2337/db13-1901
[79]	Zhang JW, Luo Y, WangYH, He LJ, Li MY, Wang X. MicroRNA regulates animal adipocyte differentiation. Hereditas(Beijing), 2015, 37(12): 1175-1184.
	张进威, 罗毅, 王宇豪, 何刘军, 李明洲, 王讯. MicroRNA调控动物脂肪细胞分化研究进展. 遗传, 2015, 37(12): 1175-1184.
[80]	Mori M, Nakagami H, Rodriguez-Araujo G, Nimura K, Kaneda Y. Essential role for miR-196a in brown adipogenesis of white fat progenitor cells. PLoS Biol, 2012, 10(4): 1001314.
[81]	Chen Y, Siegel F, Kipschull S, Haas B, Fröhlich H, Meister G, Pfeifer A. miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit. Nat Commun, 2013, 4(1): 1769. doi: 10.1038/ncomms2742
[82]	Zhang HB, Guan MP, Townsend KL, Huang TL, An D, Yan X, Xue RD, Schulz TJ, Winnay J, Mori M, Hirshman MF, Kristiansen K, Tsang JS, White AP, Cypess AM, Goodyear LJ, Tseng Y-H. Micro RNA-455 regulates brown adipogenesis via a novel HIF 1an-AMPK-PGC 1α signaling network. EMBO Rep, 2015, 16(10): 1378-1393. doi: 10.15252/embr.201540837
[83]	Ng R, Hussain NA, Zhang QY, Chang CW, Li HY, Fu YY, Cao L, Han WP, Stunkel W, Xu F. miRNA-32 drives brown fat thermogenesis and trans-activates subcutaneous white fat browning in mice. Cell Rep, 2017, 19(6): 1229-1246. doi: S2211-1247(17)30529-6 pmid: 28494871
[84]	Fu T, Seok S, Choi S, Huang Z, Suino-Powell K, Xu HE, Kemper B, Kemper JK. MicroRNA 34a inhibits beige and brown fat formation in obesity in part by suppressing adipocyte fibroblast growth factor 21 signaling and SIRT1 function. Mol Cell Biol, 2014, 34(22): 4130-4142. doi: 10.1128/MCB.00596-14 pmid: 25182532
[85]	Giroud M, Karbiener M, Pisani DF, Ghandour RA, Beranger GE, Niemi T, Taittonen M, Nuutila P, Virtanen KA, Langin D, Scheideler M, Amri E-Z. Let-7i-5p represses brite adipocyte function in mice and humans. Sci Rep, 2016, 6(1): 28613. doi: 10.1038/srep28613
[86]	Hu F, Wang M, Xiao T, Yin BQ, He LY, Meng W, Dong MJ, Liu F.miR-30 promotes thermogenesis and the development of beige fat by targeting RIP140. Diabetes, 2015, 64(6): 2056-2068. doi: 10.2337/db14-1117 pmid: 25576051
[87]	Giroud M, Pisani DF, Karbiener M, Barquissau V, Ghandour RA, Tews D, Fischer-Posovszky P, Chambard J-C, Knippschild U, Niemi T, Taittonen M, Nuutila P, Wabitsch M, Herzig S, Virtanen KA, Langin D, Scheideler M, Amri E-Z. miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function. Mol Metab, 2016, 5(8): 615-625. doi: S2212-8778(16)30058-8 pmid: 27656399
[88]	Rocha AL, De Lima TI, De Souza GP, Corrêa RO, Ferrucci DL, Rodrigues B, Lopes-Ramos C, Nilsson D, Knittel TL, Castro PR, Fernandes MF, Martins FDS, Parmigiani RB, Silveira LR, Carvalho HF, Auwerx J, Vinolo MAR, Boucher J, Mori MA. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. Sci Adv, 2020, 6(49): 1-15.
[89]	Cui TT, Xing TY, Chu YK, Li H, Wang N. Genetic and epigenetic regulation of PPARγ during adipogenesis. Hereditas (Beijing), 2017, 39(11):1066-1077.
	崔婷婷, 邢天宇, 褚衍凯, 李辉, 王宁. PPARγ 在脂肪生成中的遗传和表观遗传调控. 遗传, 2017, 39(11): 1066-1077.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

表观修饰	酶的名称	染色质标记	功能	参考文献
DNA甲基化	DNMT1/DNMT3A	DNA甲基化	促进分化	[12]
DNA甲基化	DNMT3B	DNA甲基化	抑制产热、促进分化	[13,14]
DNA去甲基化	TET1/2/3	DNA去甲基化	促进分化、促进产热、抑制米色化	[15~17]
组蛋白乙酰化	GCN5/PCAF	H3K9Ac	促进米色化、促进分化	[18,19]
组蛋白乙酰化	CBP/p300	H3K27Ac	促进分化	[20]
组蛋白去乙酰化	HDAC1	H3K27Ac	抑制产热	[21,22]
	HDAC3	H3K27Ac、去乙酰化非组蛋白	抑制产热、抑制米色化、促进产热	[23~25]
	HDAC9	H3K27Ac	抑制米色化	[26]
	SIRT1	H3K9Ac、H4K16Ac、去乙酰化非组蛋白	抑制分化、促进米色化	[27~29]
	SIRT2	H3K9Ac	抑制分化	[30]
	SIRT5	H3K9Ac	促进米色化	[31]
	SIRT6	H3K9Ac	促进分化、促进产热	[32,33]
	SIRT7	H3K9Ac、H4K16Ac	促进分化	[34]
组蛋白甲基化	MLL3/4	H3K4me1/me2	促进分化、促进产热	[353637]
	EHMT1	H3K9me1/me2	促进分化	[38]
	EHMT2	H3K9me2	抑制分化	[39,40]
	EZH2	H3K27me3	促进分化、抑制分化	[41,42]
	NSD2	H3K36me1/me2	促进分化	[43]
	KMT5B/KMT5C	H4K20me3	抑制产热、促进产热	[44,45]
组蛋白去甲基化	LSD1	H3K4me1/me2、H3K9me1/me2	促进分化、促进氧化磷酸化、促进产热	[46,47,48,49]
	KDM3A	H3K9me1/me2	促进产热	[50,51]
	KDM6A	H3K27me3	促进分化、促进产热	[12,52]
	KDM6B	H3K27me3	促进产热	[53]

表观遗传修饰对脂肪组织产热的调控进展

Progress on the epigenetic regulation of adipose tissue thermogenesis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 89

相关文章 12

编辑推荐

Metrics

[1]	曲卉, 柳毅, 陈雅文, 汪晖. 环境因素所致印迹基因改变与子代器官发育[J]. 遗传, 2022, 44(2): 107-116.
[2]	张杨景晖, 常沛瑶, 杨紫淑, 薛宇航, 李雪奇, 张旸. 表观遗传修饰影响花青苷合成研究进展[J]. 遗传, 2022, 44(12): 1117-1127.
[3]	王雅楠, 徐涛, 王万鹏, 张庆祝, 解莉楠. 表观遗传修饰在作物重要性状形成中的作用[J]. 遗传, 2021, 43(9): 858-879.
[4]	吴杰, 全建平, 叶勇, 吴珍芳, 杨杰, 杨明, 郑恩琴. 染色质转座酶可及性测序研究进展[J]. 遗传, 2020, 42(4): 333-346.
[5]	黎伟, 秦俊, 汪晖, 陈廖斌. 表观遗传生物标志物在人类疾病早期诊治中的研究进展[J]. 遗传, 2018, 40(2): 104-115.
[6]	李书粉,李莎,邓传良,卢龙斗,高武军. 转座子在植物XY性染色体起源与演化过程中的作用[J]. 遗传, 2015, 37(2): 157-164.
[7]	陈利, 丁芳, 刘勇, 吴风瑞, 丁彪, 王荣, 李文雍. 小鼠孤雌胚、体外培养胚与体内胚H3K9乙酰式的比较[J]. 遗传, 2015, 37(1): 77-83.
[8]	葛少钦, 赵峥辉, 张雪倩, 郝媛. 精子表观遗传修饰及其在胚胎发育过程中的潜在作用[J]. 遗传, 2014, 36(5): 439-446.
[9]	潘丽娜. 表观遗传修饰调控非生物胁迫应答提高植物抗逆性的研究进展[J]. 遗传, 2013, 35(6): 745-751.
[10]	王学耕朱作言孙永华赵珏. 鱼类核移植与重编程[J]. 遗传, 2013, 35(4): 433-440.
[11]	郭磊，李慧，韩之明. DNA甲基化和组蛋白修饰在克隆动物发育过程中的作用[J]. 遗传, 2010, 32(8): 762-768.
[12]	曹更生，张洪，周文平，李宁 . 免疫荧光染色检测克隆牛X染色体组蛋白H3 Lys 4 二甲基化修饰[J]. 遗传, 2009, 31(6): 611-614.