PPAR-γ Agonist Ameliorates Liver Pathology Accompanied by Increasing Regulatory B and T Cells in High-Fat-Diet Mice
PPAR-γ Agonist Ameliorates Liver Pathology Accompanied by Increasing Regulatory B and T Cells in High-Fat-Diet Mice
复制标题
PPAR-γ 激动剂可改善高脂肪饮食小鼠的肝脏病理，同时增加调节性 B 细胞和 T 细胞。
作者：
Xu, Zhipeng;Wang, Gang;Fu, Zan
目的：过氧化物酶体增殖物激活受体(PPAR)-γ在人类代谢紊乱中起重要作用。然而，其机制仍不完全清楚。调节细胞参与了这些代谢的改善；因此，研究了PPAR-c激动剂是否调节调节细胞。方法：C57BL/6J小鼠接受正常或高脂饮食(HFD)加或不加吡格列酮治疗。处死小鼠，检测代谢参数。采集脾和内脏脂肪组织(VAT)淋巴细胞，用流式细胞仪分析ST2(+)Tregs和Bregs。用免疫荧光法和酶联免疫吸附试验检测肝脏和VAT中IL-10的含量。用Pearson相关分析进行IL-10与肝脏重量和血清总胆固醇的相关性分析。结果：吡格列酮增加VAT重量，降低血清总胆固醇、肝脏脂肪变性和胆固醇结晶。吡格列酮治疗可增加高脂饮食小鼠VAT和脾中ST2(+)Tregs和Bregs的表达(均P<0.05)。吡格列酮治疗可增加高脂饲料喂养小鼠肝脏或VAT中IL-10的含量(均P<0.05)。服用吡格列酮的HFD小鼠肝脏IL-10的表达与肝脏重量和血清总胆固醇呈显著负相关(r(2)=0.74，P<；0.05；r(2)=0.58，P<；0.05)。结论：PPAR-γ信号通路通过促进调节细胞反应在代谢紊乱的调节中发挥重要作用。
Objective: Peroxisome proliferator-activated receptor ( PPAR)- gamma plays critical roles in human metabolic disorders. However, the mechanism remains incompletely understood. Regulatory cells contribute to these metabolic improvements; therefore, whether PPAR-c agonist regulates regulatory cells was investigated.Methods: C57BL/6J mice received a normal or high-fat diet (HFD) with or without pioglitazone treatment. Mice were sacrificed for detecting the metabolic parameters. Lymphocytes from spleen and visceral adipose tissue (VAT) were collected and analyzed for ST2(+)Tregs and Bregs by flow cytometry. IL-10 in the liver or VAT was detected by immunofluorescence and ELISA. Correlation analysis between IL-10 and liver weight or serum total cholesterol was made by Pearson correlation analysis.Results: Pioglitazone increased VAT weight but reduced serum total cholesterol, hepatic steatosis, and cholesterol crystallization formation. Pioglitazone treatment enhanced ST2(+)Tregs and Bregs in the VAT and spleen of HFD-fed mice (all P < 0.05). Pioglitazone treatment increased IL-10 in the livers or VAT of HFD-fed mice ( all P < 0.05). The expression of IL-10 in the liver was significantly negatively correlated with liver weight or serum total cholesterol in pioglitazone-treated HFD-fed mice (r(2) = 0.74, P < 0.05; r(2) = 0.58, P < 0.05).Conclusions: PPAR-gamma signaling plays a critical role in the regulation of metabolic disorders through promoting regulatory cell response.