Department of Pain, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China.
Department of Anesthesiology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
Biochem Biophys Res Commun. 2019 Mar 26;511(1):41-48. doi: 10.1016/j.bbrc.2019.01.058. Epub 2019 Feb 11.
High fat diet (HFD)-induced obesity is associated with insulin resistance (IR) and other chronic, diet associated illnesses, including neuroinflammation and brain injury. However, the involvement of inflammatory response in HFD-elicited central nerve injury has yet to be fully determined. Recent studies have indicated that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS), also known as TRPC4AP, plays an essential role in regulating inflammation via the meditation of NF-κB signaling. In the present study, we attempted to explore the effects of TRUSS on HFD-induced brain injury in the wild type mice (TRUSS) or TRUSS-knockout mice (TRUSS). The results suggested that TRUSS deletion attenuated HFD-induced cognitive impairments in mice. HFD-elicited metabolic disorders were also highly improved by the loss of TRUSS, as evidenced by the reduced serum glucose and insulin levels, as well as the lipid deposition in liver tissues. In addition, HFD-triggered brain injury was markedly alleviated by the TRUSS ablation, as proved by the reduction of GFAP and Iba1 expressions in hippocampus and hypothalamus. Moreover, TRUSS mice exhibited a significant decrease in the expression of pro-inflammatory cytokines, accompanied with the inactivation of IKKα/IκBα/NF-κB pathway. At the same time, HFD-induced dyslipidemia was also alleviated by the loss of TRUSS. The in vitro study verified the protective effects of TRUSS-suppression against HFD-induced central nerve injury and hepatic steatosis by restraining the inflammatory response. In summary, our data indicated that TRUSS participated in metabolic syndrome-induced brain injury and pointed to the repression of TRUSS as a promising strategy for cognitive deficits therapy.
高脂肪饮食（HFD）诱导的肥胖与胰岛素抵抗（IR）和其他慢性、饮食相关疾病有关，包括神经炎症和脑损伤。然而，炎症反应在 HFD 引起的中枢神经损伤中的参与尚未完全确定。最近的研究表明，肿瘤坏死因子受体相关普遍支架和信号蛋白（TRUSS），也称为 TRPC4AP，通过调节 NF-κB 信号在炎症反应中发挥重要作用。在本研究中，我们试图探讨 TRUSS 对野生型小鼠（TRUSS）或 TRUSS 敲除小鼠（TRUSS）中 HFD 诱导的脑损伤的影响。结果表明，TRUSS 缺失可减轻 HFD 诱导的小鼠认知障碍。TRUSS 的缺失也极大地改善了 HFD 引起的代谢紊乱，表现为血清葡萄糖和胰岛素水平降低，以及肝组织脂质沉积减少。此外，TRUSS 消融显著减轻了 HFD 引发的脑损伤，这一点可以从海马体和下丘脑 GFAP 和 Iba1 表达的减少得到证明。此外，TRUSS 小鼠表现出促炎细胞因子表达的显著减少，伴随着 IKKα/IκBα/NF-κB 通路的失活。同时，TRUSS 的缺失也减轻了 HFD 引起的血脂异常。体外研究证实了 TRUSS 抑制通过抑制炎症反应对 HFD 诱导的中枢神经损伤和肝脂肪变性具有保护作用。总之，我们的数据表明，TRUSS 参与了代谢综合征引起的脑损伤，并指出抑制 TRUSS 可能是治疗认知功能障碍的一种有前途的策略。
