J Diabetes Complications. 2023 Jun;37(6):108479.doi: 10.1016/j.jdiacomp.2023.108479. Epub 2023 Apr 21.

本文采用的英格恩产品: 增强型ECL发光液

PSTPIP2 alleviates obesity associated adipose tissue inflammation and insulin resistance in diabetes mice through promoting M2 macrophage polarization via activation of PPARγ

Affiliations

Affiliations

  • 1 Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China. Electronic address: jing_xu1207@163.com.
  • 2 Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.

Abstract

Background: Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) plays a role in inflammatory disease. In diabetes, very little is known about PSTPIP2 until now. Hence, this study aimed to determine PSTPIP2 functional role in diabetes.

Methods: Diabetes mouse model was constructed by feeding high fat diet (HFD). Intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were examined the glucose and insulin tolerance. The expression of genes and proteins was detected by quantitative real time PCR, immunohistochemistry and western blotting. The pathological changes of epididymal adipose tissues were examined by hematoxylin-eosin staining. RAW264.7 macrophages were treated with GW9662 (PPARγ antagonist). Flow cytometry examined the proportion of M1/M2 macrophages.

Results: HFD enhanced the body weight, glucose and insulin tolerance, and inhibited PSTPIP2 expression in mice. PSTPIP2 overexpression alleviated glucose and insulin tolerance, reduced inflammation and macrophage accumulation in the epididymal adipose tissues of diabetic mice. The expression of iNOS and TNF-α was increased, the expression of IL-10 and Arg-1 was decreased in diabetic mice, which was abrogated by PSTPIP2 overexpression. In vitro, PSTPIP2 overexpression reduced the proportions of iNOS-positive cells and enhanced the proportions of CD206-positive cells in RAW264.7 cells. PPARγ and p-STAT6 were up-regulated, STAT6 was down-regulated in RAW264.7 cells. GW9662 impaired PSTPIP2 overexpression-mediated up-regulation of Arg-1, YM-1 and FIZZ1 in RAW264.7 cells.

Conclusion: PSTPIP2 alleviates obesity associated adipose tissue inflammation and insulin resistance in diabetic mice through promoting M2 macrophage polarization via activation of PPARγ, suggesting that PSTPIP2 is a prospective target for diabetes treatment.

Keywords: Diabetes; Insulin resistance; Macrophage polarization; PPARγ; PSTPIP2.

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