C1q/TNF-related protein 4 restores leptin sensitivity by downregulating NF-kappa B signaling and microglial activation

作者全名："Ye, Liu; Jia, Gongwei; Li, Yuejie; Wang, Ying; Chen, Hong; Yu, Lehua; Wu, Dandong"

作者地址："[Ye, Liu; Jia, Gongwei; Li, Yuejie; Wang, Ying; Yu, Lehua; Wu, Dandong] Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Chen, Hong] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Wu, DD (corresponding author), Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：JOURNAL OF NEUROINFLAMMATION

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000677601000001

JCR分区：Q1

影响因子：9.3

年份：2021

卷号：18

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：CTRP4; Leptin signaling; Microglial activation; NE-kappa B signaling; Diet-induced obesity

摘要："Objective: C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO. Methods: Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-alpha and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-kappa B signaling cascade and microglial activation were also examined in viva In addition, NF-kappa B signaling and proinflammatory factors were investigated in BV-2 cells after CTRP4 intervention. Results: We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-alpha and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-kappa B signaling and microglial activation were also significantly suppressed in vivo. In addition, NE-kappa B signaling was inhibited in BV-2 cells following CTRP4 intervention, which was consistent with the decreased production of TNF-alpha and IL-6. Conclusions: Our data indicate that CTRP4 reverses leptin resistance by inhibiting NE-kappa B-dependent microglial activation and hypothalamic inflammation."

基金机构："Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81600615, 82072543]"

基金资助正文：This study was funded by the Natural Science Foundation of China (No. 81600615 and No. 82072543).