多巴胺D2受体基因敲除导致体重减轻以及棕色脂肪PRDM16、UCP1、FAS和ACC的表达变化#br#

doi:10.13418/j.issn.1001-165x.2019.03.008

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (3) : 278-281. DOI: 10.13418/j.issn.1001-165x.2019.03.008

实验研究

多巴胺D2受体基因敲除导致体重减轻以及棕色脂肪PRDM16、UCP1、FAS和ACC的表达变化#br#

张毅敏^{1, 2, 3}，　连辉^{1, 2, 3}，　付升旗^{1, 2, 3}，　宋海岩^{1, 2, 3}，　毛康⁴

作者信息 +

Changes of PRDM16, UCP1, FAS and ACC expression of dopamine D2 receptor knockout mice

ZHANG Yi-min^{1, 2, 3}, LIAN Hui^{1, 2, 3}, FU Sheng-qi^{1, 2, 3}, SONG Hai-yan^{1, 2, 3}, MAO Kang⁴

Author information +

文章历史 +

摘要

目的　以多巴胺D2受体基因敲除（D2KO）小鼠为动物模型，研究D2KO小鼠体重减轻后，棕色脂肪组织（brown adipose tissue，BAT）重量，白色脂肪重量，BAT中含PR结构域蛋白16（PRD1-BF1-RIZ1 homologous domain containing 16，PRDM16）、解偶联蛋白1（uncoupling protein 1，UCP1）、脂肪酸合酶（fatty acid synthase，FAS）以及乙酰辅酶A羧化酶（acetyl Coenzyme A carboxylase，ACC）的mRNA和蛋白表达变化，以期为肥胖机制研究提供线索。方法　8周龄野生型小鼠组（wild type，WT）和D2KO小鼠组各10只。分别称量各小鼠体重及其白色脂肪、棕色脂肪重量。Real-time quantitative RT-PCR方法检测棕色脂肪中PRDM16、UCP1、FAS、ACC的mRNA表达水平，Western blotting方法检测棕色脂肪中PRDM16、UCP1、FAS、ACC的蛋白表达水平。结果　WT组动物体重为（23.78±0.54）g，D2KO组动物体重为（20.54±1.15）g，P＜0.05。WT组动物附睾脂肪（epididymal adipose tissue，eAT）重量为（1.083±0.02）g，D2KO组动物eAT重量为（0.978±0.03）g，P＜0.05。WT组动物皮下脂肪（subcutaneous adipose tissue，sAT）重量为（1.85±0.05）g，D2KO组动物sAT重量为（1.72±0.03）g，P<0.05。WT组动物BAT重量为（31.38±4.22）mg，D2KO组动物BAT重量为（42.44±2.47）mg，P<0.05。半定量PCR与Western blotting检测结果显示，相对于WT组，D2KO组小鼠棕色脂肪中PRDM16、FAS、ACC的mRNA与蛋白的表达均显著增加，UCP1的mRNA与蛋白表达显著减少。结论　D2KO小鼠的体重减轻与棕色脂肪中的PRDM16、UCP1、FAS以及ACC存在一定关联。

Abstract

Objective　To observe the expression of PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), uncoupling protein 1 (UCP1), fatty acid synthase (FAS) and acetyl Coenzyme A carboxylase (ACC) in dopamine D2 receptor knockout mice.　Methods　The body weight and fat mass of wild type group (WT) and dopamine D2 receptor knockout group (D2KO) were compared. Real-time quantitative RT-PCR and Western blotting analysis were used to detect PRDM16, UCP1, FAS and ACC expression in BAT of both groups.　Results　Body weight of the WT group was (23.78±0.54) g while D2KO group was (20.54±1.15) g. The epididymal adipose tissue (eAT) fat mass was (1.083±0.02) g while the D2KO group was (0.978±0.03) g. The subcutaneous adipose tissue (sAT) fat mass was (1.85±0.05) g while the D2KO group was (1.72±0.03) g. The brown adipose tissue (BAT) fat mass was (31.38±4.22) mg while the D2KO group was (42.44±2.47) mg. Compared with the WT group, the mRNA and protein expression of UCP1 in BAT were significantly decreased in D2KO group while the mRNA and protein expression of PRDM16, FAS, ACC were significantly increased. The mRNA and protein level of ACC did not change between two groups. Conclusion　The expression of PRDM16, UCP1, FAS and ACC in BAT may be related to the weight loss of dopamine D2 receptor knockout mice. Compared with the WT group, the mRNA and protein expression of UCP1 in BAT is significantly decreased in D2KO group while the mRNA and protein expression of PRDM16, FAS, ACC is significantly increased.

导出引用

张毅敏, 连辉, 付升旗, 宋海岩, 毛康. 多巴胺D2受体基因敲除导致体重减轻以及棕色脂肪PRDM16、UCP1、FAS和ACC的表达变化#br#[J]. 中国临床解剖学杂志. 2019, 37(3): 278-281 https://doi.org/10.13418/j.issn.1001-165x.2019.03.008

ZHANG Yi-min, LIAN Hui, FU Sheng-qi, SONG Hai-yan, MAO Kang. Changes of PRDM16, UCP1, FAS and ACC expression of dopamine D2 receptor knockout mice[J]. Chinese Journal of Clinical Anatomy. 2019, 37(3): 278-281 https://doi.org/10.13418/j.issn.1001-165x.2019.03.008

中图分类号： R322.85 R354

参考文献

[1] Kenny PJ, Voren G, Johnson PM. Dopamine D2 receptors and striatopallidal transmission in addiction and obesity[J]. Curr Opin Neurobiol, 2013, 23(4): 535-538.　
[2] Kravitz AV, O’Neal TJ, Friend DM. Do dopaminergic impairments underlie physical inactivity in people with obesity[J]. Front Hum Neurosci, 2016, 10: 514.
[3] Kok P, Roelfsema F, Frölich M, et al. Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women [J]. Am J Physiol Endocrinol Metab, 2006, 291(5): E1038-1043.
[4] Dang LC, Samanez-Larkin GR, Castrellon JJ, et al. Associations between dopamine D2 receptor availability and BMI depend on age[J]. Neuroimage, 2016, 138: 176-183.
[5] Benton D, Young HA. A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food Addiction[J]. Int J Obes, 2016, 40 (Suppl 1): S12-S21.
[6] Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans[J]. N Engl J Med, 2009, 360(15): 1509-1517.
[7] Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults[J]. N Engl J Med, 2009, 360(15): 1518-1825.
[8] Villarroya F, Cereijo R, Villarroya J, et al. Brown adipose tissue as a secretory organ[J]. Nat Rev Endocrinol, 2017, 13(1): 26-35.
[9] Beeler JA, Faust RP, Turkson S, et al. Low dopamine D2 receptor increases vulnerability to obesity via reduced physical activity not increased appetitive motivation[J]. Biol Psychiatry, 2016, 79(11): 887-897.
[10] Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adulthumans[J]. Am J Physiol Endocrinol Metab, 2007, 293(2): E444-E452.
[11] Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16[J]. Cell Metab, 2007, 6(1): 38-54.
[12] Sugimoto S, Nakajima H, Kodo K, et al. Miglitol increases energy expenditure by upregulating uncoupling protein 1 of brown adipose tissue and reduces obesity in dietaryinduced obese mice[J]. Nutr Metab, 2014, 11(1): 14.
[13]Sell H, Deshaies Y, Richard D. The brown adipocyte: update on its metabolic role[J]. Int J Biochem CellBiol, 2004, 36(11): 2098-2104.
[14] Ameer F, Scandiuzzi L, Hasnain S, et al. De novo lipogenesis in health and disease[J]. Metabolism, 2014, 63(7): 895-902.
[15]Solinas G, Borén J, Dulloo AG. De novo lipogenesis in metabolic homeostasis: more friend than foe[J]. Mol Metab, 2015, 4(5): 367-377.