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

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

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1μmol/L罗格列酮)和Rosi-2组(加入2μmol/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。

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.