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过氧化物酶体增殖物激活受体γ激动剂可改善高脂肪饮食诱导的小鼠肝组织病理学改变,同时增加调节性 B 和 T 细胞数量。

PPAR-γ agonist ameliorates liver pathology accompanied by increasing regulatory B and T cells in high-fat-diet mice.

机构信息

Department of Pathogen Biology and Immunology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.

Department of Common Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.

出版信息

Obesity (Silver Spring). 2017 Mar;25(3):581-590. doi: 10.1002/oby.21769. Epub 2017 Feb 2.

DOI:10.1002/oby.21769
PMID:28150448
Abstract

OBJECTIVE

Peroxisome proliferator-activated receptor (PPAR)-γ plays critical roles in human metabolic disorders. However, the mechanism remains incompletely understood. Regulatory cells contribute to these metabolic improvements; therefore, whether PPAR-γ 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  = 0.74, P < 0.05; r  = 0.58, P < 0.05).

CONCLUSIONS

PPAR-γ signaling plays a critical role in the regulation of metabolic disorders through promoting regulatory cell response.

摘要

目的

过氧化物酶体增殖物激活受体(PPAR)-γ 在人类代谢紊乱中发挥关键作用。然而,其机制仍不完全清楚。调节细胞有助于改善这些代谢紊乱;因此,研究了 PPAR-γ 激动剂是否调节调节细胞。

方法

C57BL/6J 小鼠接受正常或高脂肪饮食(HFD),并接受或不接受吡格列酮治疗。处死小鼠以检测代谢参数。收集来自脾脏和内脏脂肪组织(VAT)的淋巴细胞,并通过流式细胞术分析 ST2 Treg 和 Breg。通过免疫荧光和 ELISA 检测肝脏或 VAT 中的 IL-10。通过 Pearson 相关分析进行 IL-10 与肝重或血清总胆固醇之间的相关性分析。

结果

吡格列酮增加了 VAT 重量,但降低了血清总胆固醇、肝脂肪变性和胆固醇结晶形成。吡格列酮治疗增强了 HFD 喂养小鼠 VAT 和脾脏中的 ST2 Treg 和 Breg(均 P < 0.05)。吡格列酮治疗增加了 HFD 喂养小鼠肝脏或 VAT 中的 IL-10(均 P < 0.05)。在接受吡格列酮治疗的 HFD 喂养小鼠中,肝脏中 IL-10 的表达与肝重或血清总胆固醇呈显著负相关(r = 0.74,P < 0.05;r = 0.58,P < 0.05)。

结论

PPAR-γ 信号通过促进调节性细胞反应在调节代谢紊乱中发挥关键作用。

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