早衰小鼠棕色脂肪组织的切伦科夫光学显像及代谢活性变化
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摘要
目的探讨切伦科夫光学显像在棕色脂肪组织代谢研究中的应用价值,并评估早衰小鼠棕色脂肪组织的代谢活性变化。方法以早衰小鼠为研究模型,采用切伦科夫光学成像动态监测早衰小鼠棕色脂肪组织代谢活性的变化,以~(18)F-FDG PET/CT成像为参照;通过检测棕色脂肪组织活性分子标志物解偶联蛋白酶1(uncoupling protein 1,UCP1)的转录和蛋白表达水平评估早衰小鼠棕色脂肪组织衰老情况。结果 4～12周龄时,早衰小鼠棕色脂肪组织SUV_(max)及切伦科夫光学显像光强度值未见明显变化(P>0.05),14周龄时早衰小鼠棕色脂肪组织PET/CT成像最大摄入值(SUV_(max))、切伦科夫光强度值较12周龄时均显著下降(P<0.01)。分子水平上早衰小鼠UCP1的mRNA水平于12周龄开始下降(P<0.05),而蛋白表达水平在14周龄时显著下降(P<0.01),与显像结果一致。结论切伦科夫光学显像能够有效评估小鼠棕色脂肪组织代谢活性;早衰小鼠14周龄即出现棕色脂肪组织代谢活性的减退。
Objective To study the changes in the metabolic activity of brown adipose tissues in a mouse model of progeria using Cerenkov luminescence imaging. Methods18 F-FDG PET/CT imaging and Cerenkov luminescence imaging were used to dynamically monitor the metabolic activity of the brown adipose tissue in progeria mice. The ageing of the brown adipose tissue was evaluated by detecting the transcriptional and protein expression levels of uncoupling protein 1( UCP1),a molecular marker of brown adipose tissue activity. Results At 4 to 12 weeks of age,the progeria mice showed no obvious changes in the SUVm ax and Cerenkov luminescence imaging light intensity in the brown adipose tissue( P>0.05). At 14 weeks of age,the SUVm ax and Cerenkov imaging light intensity in the brown adipose tissue were decreased significantly in progeria mice( P<0.01). At the molecular level,the mRNA expression level of UCP1 began to decrease in the progeria mice at 12 weeks( P<0.05),while UCP1 protein expression level decreased significantly at 14 weeks of age( P < 0. 01),which were consistent with the results of the imaging studies. Conclusion Cerenkov luminescence imaging allows efficient assessment of the changes in the metabolic activity of the brown adipose tissue in mice. In progeria mice,the metabolic activity of the brown adipose tissue becomes lowered as early as14 weeks of age.
Objective To study the changes in the metabolic activity of brown adipose tissues in a mouse model of progeria using Cerenkov luminescence imaging. Methods18 F-FDG PET/CT imaging and Cerenkov luminescence imaging were used to dynamically monitor the metabolic activity of the brown adipose tissue in progeria mice. The ageing of the brown adipose tissue was evaluated by detecting the transcriptional and protein expression levels of uncoupling protein 1( UCP1),a molecular marker of brown adipose tissue activity. Results At 4 to 12 weeks of age,the progeria mice showed no obvious changes in the SUVm ax and Cerenkov luminescence imaging light intensity in the brown adipose tissue( P>0.05). At 14 weeks of age,the SUVm ax and Cerenkov imaging light intensity in the brown adipose tissue were decreased significantly in progeria mice( P<0.01). At the molecular level,the mRNA expression level of UCP1 began to decrease in the progeria mice at 12 weeks( P<0.05),while UCP1 protein expression level decreased significantly at 14 weeks of age( P < 0. 01),which were consistent with the results of the imaging studies. Conclusion Cerenkov luminescence imaging allows efficient assessment of the changes in the metabolic activity of the brown adipose tissue in mice. In progeria mice,the metabolic activity of the brown adipose tissue becomes lowered as early as14 weeks of age.
引文
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[3] KOKSHAROVA E,USTYUZHANIN D,PHILIPPOV Y,et al.The relationship between brown adipose tissue content in supraclavicular fat depots and insulin sensitivity in patients with type 2 diabetes mellitus and prediabetes[J].Diabetes Technol Ther,2017,19(2):96-102.DOI:10.1089/dia.2016.0360.
[4] HOEKE G,KOOIJMAN S,BOON M R,et al.Role of brown fat in lipoprotein metabolism and atherosclerosis[J].Circ Res,2016,118(1):173-182.DOI:10.1161/CIRCRESAHA.115.306647.
[5] SUN J J,ZHANG L P,SUN R C,et al.Exploring the influence of resiliency on physician trust in patients:An empirical study of Chinese incidents[J].PLoS ONE,2018,13(12):e0207394.DOI:10.1371/journal.pone.0207394.
[6] COHEN P,SPIEGELMAN B M.Cell biology of fatstorage[J].Mol Biol Cell,2016,27(16):2523-2527.DOI:10.1091/mbc.e15-10-0749.
[7] SUN L,YAN J,SUN L,et al.A synopsis of brown adipose tissue imaging modalities for clinical research[J].Diabetes Metab,2017,43(5):401-410.DOI:10.1016/j.diabet.2017.03.008.
[8] CRANDALL J P,JOO H O,GAJWANI P,et al.Measurement of brown adipose tissue activity using microwave radiometry and 18F-FDG PET/CT[J].J Nucl Med,2018,59(8):1243-1248.DOI:10.2967/jnumed.117.204339.
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[10] JUNG H J,COFFINIER C,CHOE Y,et al.Regulation of prelamin A but not lamin C by miR-9,a brain-specific microRNA[J].Proc Natl Acad Sci USA,2012,109(7):E423-E431.DOI:10.1073/pnas.1111780109.
[11] GAO Y H,MA X W,KANG F,et al.Enhanced Cerenkov luminescence tomography analysis based on Y2O3:Eu3+ rare earth oxide nanoparticles[J].Biomed Opt Express,2018,9(12):6091-6102.DOI:10.1364/BOE.9.006091.
[12] LóPEZ-OTíN C,BLASCO M A,PARTRIDGE L,et al.The hallmarks of aging[J].Cell,2013,153(6):1194-1217.DOI:10.1016/j.cell.2013.05.039.
[13] KISSIG M,SHAPIRA S N,SEALE P.SnapShot:brown and beige adipose the rmogenesis[J].Cell,2016,166(1):258-258.e1.DOI:10.1016/j.cell.2016.06.038.
[14] SOLA-CARVAJAL A,REVêCHON G,HELGADOTTIR H T,et al.Accumulation of progerin affects the symmetry of cell division and is associated with impaired Wnt signaling and the mislocalization of nuclear envelope proteins[J].J Invest Dermatol,2019..DOI:10.1016/j.jid.2019.05.005.
[15] CYPESS A M,HAFT C R,LAUGHLIN M R,et al.Brown fat in humans:consensus points and experimental guidelines[J].Cell Metab,2014,20(3):408-415.DOI:10.1016/j.cmet.2014.07.025.
[16] KIM K,HUANG S,FLETCHER L A,et al.Whole body and regional quantification of active human brown adipose tissue using 18F-FDG PET/CT[J].J Vis Exp,2019(146):e58469.DOI:10.3791/58469.
[17] XIONG Z M,CHOI J Y,WANG K,et al.Methylene blue alleviates nuclear and mitochondrial abnormalities inprogeria[J].Aging Cell,2016,15(2):279-290.DOI:10.1111/acel.12434.
[18] ZHANG F,HAO G Y,SHAO M L,et al.An adipose tissue atlas:an image-guided identification of human-like BAT and beige depots in rodents[J].Cell Metab,2018,27(1):252-262.e3.DOI:10.1016/j.cmet.2017.12.004.
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