视黄酸对白色脂肪棕色化作用的研究进展
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摘要
人体内的脂肪组织可分为白色脂肪组织和棕色脂肪组织,分别负责能量的储存和消耗。其中,白色脂肪有望转化为一种类似棕色脂肪的"米色脂肪",从而消耗更多能量,这一过程被称之为"白色脂肪棕色化"。白色脂肪棕色化的过程受许多机制的调控和影响,视黄酸也参与其中。视黄酸通过与过氧化物酶体增殖物激活受体及视黄酸相关受体的结合作用增加解偶联蛋白的表达,同时也能通过促进血管生成影响后代棕色脂肪的生成,从而促进白色脂肪棕色化。未来,应深入研究视黄酸对白色脂肪棕色化作用的机制,以为肥胖及相关代谢性疾病的治疗提供新方法。
Adipose tissues in human body can be divided into the white and the brown types which are responsible for energy storage and consumption respectively. The white fat is expected to transfer into a " beige fat" that resembles brown fat,thereby consuming more energy. This process is called " white adipose tissue browning". The process of the browning of white fat is regulated and influenced by multiple mechanisms. Retinoic acid is also involved with this process. It can be combined with peroxisome proliferator-activated receptor and retinoic acid receptors to increase the expression of uncoupling protein,and promote the angiogenesis as well which can contribute the browning of white adipose tissue. In the future,the mechanism of retinoic acid on browning of white fat should be studied further in order to provide a new method for the treatment of obesity and related metabolic diseases.
Adipose tissues in human body can be divided into the white and the brown types which are responsible for energy storage and consumption respectively. The white fat is expected to transfer into a " beige fat" that resembles brown fat,thereby consuming more energy. This process is called " white adipose tissue browning". The process of the browning of white fat is regulated and influenced by multiple mechanisms. Retinoic acid is also involved with this process. It can be combined with peroxisome proliferator-activated receptor and retinoic acid receptors to increase the expression of uncoupling protein,and promote the angiogenesis as well which can contribute the browning of white adipose tissue. In the future,the mechanism of retinoic acid on browning of white fat should be studied further in order to provide a new method for the treatment of obesity and related metabolic diseases.
引文
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[25]Wang QA,Tao C,Gupta RK,et al.Tracking adipogenesis during white adipose tissue development,expansion and regeneration[J].Nat Med,2013,19(10):1338-1344.
[26]Rosenwald M,Perdikari A,Rulicke T,et al.Bi-directional interconversion of brite and white adipocytes[J].Nat Cell Biol,2013,15(6):659-667.
[27]Tran KV,Gealekman O,Frontini A,et al.The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells[J].Cell Metab,2012,15(2):222-229.
[28]Min SY,Kady J,Nam M,et al.Human brite/beige adipocytes develop from capillary networks,and their implantation improves metabolic homeostasis in mice[J].Nat Med,2016,22(3):312-318.
[29]Vishvanath L,Mac Pherson KA,Hepler C,et al.Pdgfrβ+mural preadipocytes contribute to adipocyte hyperplasia induced by high-fat-diet feeding and prolonged cold exposure in adult mice[J].Cell Metab,2016,23(2):350-359.
[30]Rennert RC,Sorkin M,Januszyk M,et al.Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations[J].Stem Cell Res Ther,2014,5(3):79.
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[32]Sun K,Park J,Gupta OT,et al.Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction[J].Nat Commun,2014,5:3485.
[33]Krois CR,Vuckovic MG,Huang P,et al.RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding[J].Cell Mol Life Sci,2019[2019-03-15].http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=General Search&qid=8&SID=7EmlO5XXlgYUkbqjxbI&page=1&doc=1.[published online ahead of print Feb 20,2019].
[34]Wang B,Wang Z,de Avila JM,et al.Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling[J].FASEB J,2017,31(10):4612-4622.
[35]Kusudo T,Hashimoto M,Kataoka N,et al.CREG1 promotes uncoupling protein 1 expression and brown adipogenesis in vitro[J].J Biochem,2019,165(1):47-55.
[36]Murholm M,Isidor MS,Basse AL,et al.Retinoic acid has different effects on UCP1 expression in mouse and human adipocy tes[J].BMC Cell Biol,2013,14:41.
[2]Boss O,Farmer SR.Recruitment of brown adipose tissue as a therapy for obesity-associated diseases[J].Front Endocrinol(Lausanne),2012,3:14.
[3]Wang B,Fu X,Zhu MJ,et al.Retinoic acid inhibits white adipogenesis by disrupting GADD45A-mediated Zfp423 DNA demethylation[J].J Mol Cell Biol,2017,9(4):338-349.
[4]Giralt M,Villarroya F.White,brown,beign/brite:Different adipose cells for different functions[J].Endocrinology,2013,154(9):2992-3000.
[5]Castillo-Quan JI.From white to brown fat through the PGC-1α-dependent myokine irisin:Implications for diabetes and obesity[J].Dis Model Mech,2012,5(3):293-295.
[6]Qiang L,Wang L,Kon N,et al.Brown remodeling of white adipose tissue by SirTl-dependent deacetylation of Pparg[J].Cell,2012,150(3):620-632.
[7]Van Marken Lichtenbelt WD,Vanhommerig JW,Smulders NM,et al.Cold-activated brown adipose tissue in healthy men[J].N Engl J Med,2009,360(15):1500-1508.
[8]Ricquier D.Uncoupling protein 1 of brown adipocytes,the only uncoupler:A historical perspective[J].Front Endocrinol(Lausanne),2011,2:85.
[9]Bonet ML,Ribot J,Palou A.Lipid metabolism in mammalian tissues and its control by retinoic acid[J].Biochim Biophys Acta,2012,1821(1):177-189.
[10]Hernandez A,de Mena RM,Martin E,et al.Differences in the response of UCP1 mRNA to hormonal stimulation between rat and mouse primary cultures of brown adipocytes[J].Cell Physiol Biochem,2011,28(5):969-980.
[11]Chen W,Howell ML,Li Y,et al.Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes[J].PLo S One,2014,9(8):e100868.
[12]Pereira SE,Saboya CJ,Saunders C,et al.Serum levels and liver store of retinol and their association with night blindness in individuals with class III obesity[J].Obes Surg,2012,22(4):602-608.
[13]Theodosiou M,Laudet V,Schubert M.From carrot to clinic:An overview of the retinoic acid signaling pathway[J].Cell Mol Life Sci,2010,67(9):1423-1445.
[14]Samarut E,Fraher D,Laudet V,et al.ZebRA:An overview of retinoic acid signaling during zebrafish development[J].Biochim Biophys Acta,2015,1849(2):73-83.
[15]Zhang R,Wang Y,Li R,et al.Transcriptional factors mediating retinoic acid signals in the control of energy metabolism[J].Int JMol Sci,2015,16(6):14210-14244.
[16]Guo H,Foncea R,O'Byrne SM,et al.Lipocalin 2:A regulator of retinoid homeostasis and retinoid-mediated thermogenic activation in adipose tissue[J].J Biol Chem,2016,291(21):11216-11229.
[17]Beranger GE,Karbiener M,Barquissau V,et al.In vitro brown and"brite""beige"adipogenesis:Human cellular models and molecular aspects[J].Biochim Biophys Acta,2013,1831(5):905-914.
[18]Berry DC,Noy N.All-trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferationactivated receptor beta/delta and retinoic acid receptor[J].Mol Cell Biol,2009,29(12):3286-3296.
[19]Wener CM,Schirmer SH,Gensch C,et al.The dual PPARα/γagoinst aleglitazar increases the number and function of endothelial progentitor cells:Implications for vascular function and atherogenesis[J].Br J pharmacol,2014,171(10):2685-2703.
[20]Petrovic N,Walden TB,Shabalina IG,et al.Chronic peroxisome proliferator activated receptor gamma(PPARγgamma)activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent,UCP1-containing adipocytes molecularly distinct from classic brown adipocytes[J].J Biol Chem,2010,285(10):7153-7164.
[21]Rajakumari S,Wu J,Ishibashi J,et al.EBF2 determines and maintains brown adipocyte identify[J].Cell Metab,2013,17(4):562-574.
[22]Vernochet C,Peres SB,Davis KE,et al.C/EBPαand the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipsose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator activated receptorγagonists[J].Mol Cell Biol,2009,29(17):4714-4728.
[23]Mercader J,Ribot J,Murano I,et al.Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity,insulin resistance,and hepatosteatosis in mice[J].Am J Physiol Endocrinol Metab,2009,297(1):E184-193.
[24]Wang B,Fu X,Liang X,et al.Maternal retinoids increase PDGFRα+progenitor population and beige adipogenesis in progeny by stimulating vascular development[J].EBioMedicine,2017,18:288-299.
[25]Wang QA,Tao C,Gupta RK,et al.Tracking adipogenesis during white adipose tissue development,expansion and regeneration[J].Nat Med,2013,19(10):1338-1344.
[26]Rosenwald M,Perdikari A,Rulicke T,et al.Bi-directional interconversion of brite and white adipocytes[J].Nat Cell Biol,2013,15(6):659-667.
[27]Tran KV,Gealekman O,Frontini A,et al.The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells[J].Cell Metab,2012,15(2):222-229.
[28]Min SY,Kady J,Nam M,et al.Human brite/beige adipocytes develop from capillary networks,and their implantation improves metabolic homeostasis in mice[J].Nat Med,2016,22(3):312-318.
[29]Vishvanath L,Mac Pherson KA,Hepler C,et al.Pdgfrβ+mural preadipocytes contribute to adipocyte hyperplasia induced by high-fat-diet feeding and prolonged cold exposure in adult mice[J].Cell Metab,2016,23(2):350-359.
[30]Rennert RC,Sorkin M,Januszyk M,et al.Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations[J].Stem Cell Res Ther,2014,5(3):79.
[31]Togliatto G,Dentelli P,Gili M,et al.Obesity reduces the proangiogenic potential of adipose tissue stem cell-derived extracellular vesicles(EVs)by impairing miR-126 content:Impact on clinical applications[J].Int J Obes(Lond),2016,40(1):102-111.
[32]Sun K,Park J,Gupta OT,et al.Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction[J].Nat Commun,2014,5:3485.
[33]Krois CR,Vuckovic MG,Huang P,et al.RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding[J].Cell Mol Life Sci,2019[2019-03-15].http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=General Search&qid=8&SID=7EmlO5XXlgYUkbqjxbI&page=1&doc=1.[published online ahead of print Feb 20,2019].
[34]Wang B,Wang Z,de Avila JM,et al.Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling[J].FASEB J,2017,31(10):4612-4622.
[35]Kusudo T,Hashimoto M,Kataoka N,et al.CREG1 promotes uncoupling protein 1 expression and brown adipogenesis in vitro[J].J Biochem,2019,165(1):47-55.
[36]Murholm M,Isidor MS,Basse AL,et al.Retinoic acid has different effects on UCP1 expression in mouse and human adipocy tes[J].BMC Cell Biol,2013,14:41.