补充脱落酸或能改善高脂饮食引起的脑内炎症和胰岛素抵抗

创作:梦垚 审核:mildbreeze 10月11日
高脂饮食(HFD)大鼠的大脑海马体中,胰岛素受体底物IRS1增高、IRS2下降,TNFα和淀粉样前体蛋白APP表达增加,神经营养因子BDNF表达降低,神经生成减少;
TNFα与IRS1正相关、与IRS2负相关,APP仅与IRS1正相关;
补充脱落酸(ABA)可预防HFD诱导的记忆障碍和神经炎症,恢复海马体中上述因子的表达水平和神经生成;
结论:HFD对海马体中IRS1和IRS2的表达调控有不同影响,补充ABA可减少神经炎症和胰岛素抵抗、促进神经生成。
延伸阅读

Abscisic Acid Supplementation Rescues High Fat Diet-Induced Alterations in Hippocampal Inflammation and IRSs Expression

补充脱落酸可以改善高脂饮食引起的海马体炎症和胰岛素受体底物表达水平改变

05-02, Article, 10.1007/s12035-018-1091-zmore

Abstract:
Accumulated evidence indicates that neuroinflammation induces insulin resistance in the brain. Moreover, both processes are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Potential mechanisms underlying insulin resistance include serine phosphorylation of the insulin receptor substrate (IRS) or insulin receptor (IR) misallocation. However, only a few studies have focused on IRS expression in the brain and its modulation in neuroinflammatory processes. This study used the high-fat diet (HFD) model of neuroinflammation to study the alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS expressions in the hippocampus. We observed that HFD effectively reduced mRNA and protein IRS2 expression. In contrast, a HFD induced the upregulation of the IRS1 mRNA levels, but did not alter an IR and IGF1R expression. As expected, we observed that a HFD increased hippocampal tumor necrosis factor alpha (TNFα) and amyloid precursor protein (APP) levels while reducing brain-derived neurotrophic factor (BDNF) expression and neurogenesis. Interestingly, we found that TNFα correlated positively with IRS1 and negatively with IRS2, whereas APP levels correlated positively only with IRS1 but not IRS2. These results indicate that IRS1 and IRS2 hippocampal expression can be affected differently by HFD-induced neuroinflammation. In addition, we aimed to establish whether abscisic acid (ABA) can rescue hippocampal IRS1 and IRS2 expression, as we had previously shown that ABA supplementation prevents memory impairments and improves neuroinflammation induced by a HFD. In this study, ABA restored HFD-induced hippocampal alterations, including IRS1 and IRS2 expression, TNFα, APP, and BDNF levels and neurogenesis. In conclusion, this study highlights different regulations of hippocampal IRS1 and IRS2 expression using a HFD, indicating the important differences of these scaffolding proteins, and strongly supports ABA therapeutic effects.

First Authors:
Alberto Ribes-Navarro

Correspondence Authors:
Ana María Sánchez-Pérez

All Authors:
Alberto Ribes-Navarro,Mariam Atef,Sandra Sánchez-Sarasúa,María Teresa Beltrán-Bretones,Francisco Olucha-Bordonau,Ana María Sánchez-Pérez