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山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (9): 8-13.doi: 10.6040/j.issn.1671-7554.0.2020.0266

• 临床医学 • 上一篇    下一篇

过氧化物酶增殖物激活受体γ激动剂对24例肥胖症患者米色脂肪细胞分化的影响

李涵1,2,付婷婷1,2,张磊3,延冰3,孙涛4,郭峰5,尹晓1   

  1. 1. 山东大学附属济南市中心医院内分泌科, 山东 济南 250013;2. 山东大学齐鲁医学院, 山东 济南 250012;3. 山东大学附属济南市中心医院胃肠外科, 山东 济南 250013;4. 山东大学附属济南市中心医院两腺外科, 山东 济南 250013;5. 山东大学附属济南市中心医院泌尿外科, 山东 济南 250013
  • 出版日期:2020-09-10 发布日期:2020-08-30
  • 通讯作者: 尹晓. E-mail:2430435991@qq.com
  • 基金资助:
    国家自然科学基金(81300686)

Effects of PPARγ agonist rosiglitazone on the differentiation of beige adipocytes in 24 obese individuals

LI Han1,2, FU Tingting1,2, ZHANG Lei3, YAN Bing3, SUN Tao4, GUO Feng5, YIN Xiao1   

  1. 1.Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China;
    2. Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    3. Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China;
    4. Department of Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China;
    5. Department of Urology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
  • Online:2020-09-10 Published:2020-08-30

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摘要： 目的 探讨过氧化物酶增殖物激活受体γ(PPARγ)激动剂罗格列酮对肥胖症患者皮下白色脂肪组织的米色化的影响,为治疗肥胖症提供新的途径。 方法 选取择期手术的24例肥胖症患者皮下白色脂肪组织,分离脂肪组织基质细胞并进行成脂诱导分化,在诱导分化后期加入不同浓度的罗格列酮干预,根据干预方式的不同分为对照组、Rosi-1组(加入1 μmol/L罗格列酮)和Rosi-2组(加入2 μmol/L罗格列酮)。通过实时定量PCR法以及Western blotting法检测各组脂肪细胞中解偶联蛋白(UCP1)及米色脂肪细胞特异性产热基因的表达。通过比色法检测细胞培养液中甘油释放浓度来评估干预对脂肪细胞脂解功能的影响。 结果 加入罗格列酮干预后,Rosi-1组和Rosi-2组成熟脂肪细胞表现多脂滴外形,UCP1蛋白(t=23.12,P<0.01;t=7.35, P<0.01)和米色脂肪细胞特异性产热基因UCP1(t=2.63, P=0.03;t=9.86, P<0.01)、PPARγ(t=2.8, P=0.02;t=11.06, P<0.01)和PR16结构(PRDM16)基因(t=2.65, P=0.02;t=12.85, P<0.01)表达水平在Rosi-1组和Rosi-2组中均较对照组上调,且Rosi-1组(t=2.76, P=0.02)和Rosi-2组(t=5.83, P<0.01)的脂解能力较对照组增强。 结论 PPARγ激动剂可提高肥胖症患者白色脂肪组织的米色脂肪细胞的分化,从而促进白色脂肪组织的棕色化,选择性作用于脂肪组织的PPARγ激动剂的研发可以为肥胖症治疗提供新的途径。

关键词: 肥胖症, 过氧化物酶增殖物激活受体γ激动剂, 白色脂肪组织, 米色化, 皮下脂肪组织

Abstract: Objective To investigate the effects of peroxisome proliferators-activated receptor γ(PPARγ)agonist, rosiglitazone, on the browning process of white adipose tissues from obese patients, so as to provide possible treatment for obesity. Methods The subcutaneous white adipose tissues were collected from 24 obese patients who underwent selective operation. The adipose-derived stem cells(ADSCs)were isolated and induced to differentiate into mature adipocytes, which were then divided into control group, Rosi-1 group(1 μmol/L rosiglitazone), and Rosi-2 group(2 μmol/L rosiglitazone). The expressions of uncoupling protein 1(UCP1)and beige adipocytespecific thermogenic genes were detected with Western blotting and real time qRT-PCR. Lipolysis was analyzed using colorimetric assay. Results With rosiglitazone treatment, the adipocytes in Rosi-1 and Rosi-2 groups exhibited multi-nodular lipid droplets, higher expression of UCP1(t=23.12, P<0.01; t=7.35, P<0.01), and higher expressions of beige adipocyte specific thermogenic genes, including UCP1(t=2.63, P=0.03; t=9.86, P<0.01), PPARγ(t=2.8, P=0.02; t=11.06, P<0.01)and PRDM16(t=2.65, P=0.02; t=12.85, P<0.01). Rosi-1 group(t=2.76, P=0.02)and Rosi-2 group(t=5.83, P<0.01)showed increased lipolysis compared with control group. Conclusion PPARγ agonists can enhance the differentiation of beige adipocytes in white adipose tissues in obese patients and induce the browning process of white adipose tissues. The development of PPARγ agonists which have effects on adipose tissues may provide new path for the treatment of obesity.

Key words: Obesity, Peroxisome proliferators-activated receptor γ agonist, White adipose tissue, Browning, Subcutaneous adipose tissue

中图分类号: 

  • R589.2
[1] Mendenhall E, Singer M. The global syndemic of obesity, undernutrition, and climate change [J]. Lancet, 2019, 393(10173): 1-7.
[2] Castañeda D, Gabani M, Choi SK, et al. Targeting autophagy in obesity-associated heart disease [J]. Obesity(Silver Spring, Md.), 2019, 27(7): 1050-1058.
[3] Zeng J, Sauter ER, Li B. FABP4: A new player in obesity-associated breast cancer [J]. Trends Mol Med, 2020, 26(5): 1-4.
[4] 曹文悦,蒲迎,刘钊,等.成人脂肪细胞β3肾上腺素受体表达与肥胖的相关性[J]. 山东大学学报(医学版), 2018, 56(1): 81-85. CAO Wenyue, PU Ying, LIU Zhao, et al. Relationship between adipocyte β3 adrenergic receptor expression level and adiposity in adults [J]. Journal of Shandong University(Health Sciences), 2018, 56(1): 81-85.
[5] 金美玲, 孟凡彪, 赖奕宏, 等. 白藜芦醇抑制小鼠肥胖的功效及相关机制探讨[J]. 现代生物医学进展, 2018, 18(15): 2819-2823. JIN Meiling, MENG Fanbiao, LAI Yihong, et al. Resveratrol exerts anti-obesity effect involving modulation of UCP-1 and HO-1 [J]. Progress in Modern Biomedicine, 2018, 18(15): 2819-2823.
[6] Kim SY, Lee MS, Chang E, et al. Tartary buckwheat extract attenuated the obesity-induced inflammation and increased muscle PGC-1a/SIRT1 expression in high fat diet-induced obese rats [J]. Nutrients, 2019, 11(3): 654-667.
[7] Xie S, Li Y, Teng W. Liensinine inhibits beige adipocytes recovering to white adipocytes through blocking mitophagy flux in vitro and in vivo [J]. Nutrients, 2019, 11(7): 1640-1653.
[8] Paulo E, Wang B. Towards a better understanding of beige adipocyte plasticity [J]. Cells, 2019, 8(12): 1552-1567.
[9] Ruiz JR, Sánchez-Delgado G, Martínez-Téllez B, et al. Association between habitual physical activity and brown adipose tissue activity in individuals undergoing PET-CT scan [J]. Clin Endocrinol, 2015, 83(4): 590-594.
[10] 黄斌, 孟然, 冯斌, 等. 艾塞那肽对肥胖大鼠白色脂肪自噬及棕色化的影响[J]. 中国糖尿病杂志, 2016, 8(2): 81-86.
[11] Merlin J, Sato M, Chia LY, et al. Rosiglitazone and a β-adrenoceptor agonist are both required for functional browning of white adipocytes in culture [J]. Front Endocrinol(Lausanne), 2018, 9: 249. doi:10.3389/fendo. 2018. 00249.
[12] Narasimhan S, Weinstock RS. Youth-onset type 2 diabetes mellitus: lessons learned from the today study [J]. Mayo Clin Proc, 2014, 89(6): 806-816.
[13] Yang RZ, Lee MJ, Hu H, et al. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications [J]. PLoS Med, 2006, 3(6): 884-894.
[14] Choi SS, Park J, Choi JH. Revisiting PPARγ as a target for the treatment of metabolic disorders [J]. BMB Rep, 2014, 47(11): 599-608.
[15] Nierenberg AA, Ghaznavi SA, Sande Mathias I, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha as a novel target for bipolar disorder and other neuropsychiatric disorders [J]. Biol Psychiatry, 2018, 83(9): 761-769.
[16] Soccio RE, Li Z, Chen ER, et al. Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice [J]. J Clin Invest, 2017, 127(4): 1451-1462.
[17] Alvarez-Dominguez JR, Bai Z, Xu D, et al. De novo reconstruction of adipose tissue transcriptomes reveals long non-coding RNA regulators of brown adipocyte development [J]. Cell Metab, 2015, 21(5): 764-776.
[18] Shuai L, Zhang LN, Li BH, et al. SIRT5 Regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue [J]. Diabetes, 2019, 68(7): 1449-1461.
[19] Park SS, Lee YJ, Kang H, et al. Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling [J]. Sci Rep, 2019, 9(1): 20152. doi:10.1038/s41598-019-56817-w.
[20] Qiang L, Wang L, Kon N, et al. Brown remodeling of white adipose tissue by Sirt1-dependent deacetylation of PPARγ [J]. Cell, 2012, 150(3): 620-632.
[21] Min BK, Kang HJ, Choi BJ, et al. Phenylbutyrate ameliorates high-fat diet-induced obesity via brown adipose tissue activation [J]. Biol Pharm Bull, 2019, 42(9): 1554-1561.
[22] Bartelt A, Heeren J. Adipose tissue browning and metabolic health [J]. Nat Rev Endocrinol, 2014, 10(1): 24-36.
[23] Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management [J]. Hepatology, 2009, 49(1): 306-317.
[24] Fayyad AM, Khan AA, Abdallah SH, et al. Rosiglitazone enhances browning adipocytes in association with MAPK and PI3-K Pathways During the Differentiation of Telomerase-Transformed Mesenchymal Stromal Cells into Adipocytes [J]. Int J Mol Sci, 2019, 20(7): 1618. doi:10.3390/ijms20071618.
[25] Bae IS, Kim SH. Expression and secretion of an atrial natriuretic peptide in beige-like 3T3-L1 adipocytes [J]. Int J Mol Sci, 2019, 20(24): 6128. doi:10.3390/ijms20246128.
[26] Ross SA, Dzida G, Vora J, et al. Impact of weight gain on outcomes in type 2 diabetes [J]. Curr Med Res Opin, 2011, 27(7): 1431-1438.
[27] Eliasson B, Smith U, Mullen S, et al. Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients [J]. Adipocyte, 2014, 3(4): 314-321.
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