背景:肥胖和高脂饮食(HFD)的消耗与肠道通透性和内毒素的细胞旁转运增加有关,可以促进神经炎症。炎症可以影响下丘脑-垂体-肾上腺(HPA)轴,控制对压力的反应,下调脑源性神经营养因子(BDNF),可以促进焦虑和抑郁,肥胖中经常出现的疾病。我们以前表明,花青素(AC)的消费减轻HFD诱导的胰岛素抵抗,肠通透性,和炎症。
目的:这项工作研究了在小鼠中添加富含花青素和飞跃素提取物(CDRE)的膳食补充剂是否可以抵消HFD/肥胖诱导的海马炎症。
方法:C57BL/6J雄性小鼠饲喂14周:i)含有10%来自脂肪的总卡路里的对照饮食(C);ii)含有60%来自脂肪的总卡路里的HFD(猪油)(HF);iii)补充有2、20或40mgAC/kg体重(BW)(分别为HFA2、HFA20、HFA40)。在血浆和海马中,测定了神经炎症参数和根本原因(内毒素血症)和后果(HPA和BDNF下调的改变).
结果:HFD的消耗导致内毒素血症。因此,HF组海马Tlr4mRNA水平高110%,两者都是通过补充CDRE来预防的。HFD的消耗还引起:i)小胶质细胞增生和参与神经炎症的基因表达增加,即Iba-1、Nox4、Tnfα、和IL-1β,ii)HPA轴调节的改变,即盐皮质激素(MR)和糖皮质激素(GR)受体的低表达;和iii)Bdnf表达降低。补充HFD喂养的小鼠CDRE可减轻神经炎症,小胶质细胞增生,MR和BDNF降低。
结论:补充CDRE可减轻与小鼠海马HFD消耗和肥胖相关的负面影响,部分是通过减少炎症,改善糖皮质激素代谢,并上调BDNF。
BACKGROUND: Obesity and consumption of high-fat diets (HFD) are associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote neuroinflammation. Inflammation can affect the hypothalamic pituitary adrenal (HPA) axis, which controls responses to stress and downregulates the brain-derived neurotrophic factor (BDNF), which can promote anxiety and depression, conditions frequently found in obesity. We previously showed that consumption of anthocyanins (AC) mitigate HFD-induced insulin resistance, intestinal permeability, and inflammation.
OBJECTIVE: This study investigated if a dietary supplementation with a cyanidin- and delphinidin-rich extract (CDRE) could counteract HFD/obesity-induced hippocampal inflammation in mice.
METHODS: C57BL/6J male mice were fed for 14 wk on one of the following diets: 1) a control diet containing 10% total calories from fat (C), 2) a control diet supplemented with 40 mg AC/kg body weight (BW) (CAC), 3) a HFD containing 60% total calories from fat (lard) (HF), or 4) the HFD supplemented with 2, 20, or 40 mg AC/kg BW (HFA2, HFA20, and HFA40, respectively). In plasma and in the hippocampus, parameters of neuroinflammation and the underlying cause (endotoxemia) and consequences (alterations to the HPA and BDNF downregulation) were measured.
RESULTS: Consumption of the HFD caused endotoxemia. Accordingly, hippocampal Tlr4 mRNA levels were 110% higher in the HF group, which were both prevented by CDRE supplementation. Consumption of the HFD also caused: 1) microgliosis and increased expression of genes involved in neuroinflammation, that is, Iba-1, Nox4, Tnfα, and Il-1β, 2) alterations of HPA axis regulation, that is, with low expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors; and 3) decreased Bdnf expression. Supplementation of HFD-fed mice with CDRE mitigated neuroinflammation, microgliosis, and MR and BDNF decreases.
CONCLUSIONS: CDRE supplementation mitigates the negative effects associated with HFD consumption and obesity in mouse hippocampus, in part by decreasing inflammation, improving glucocorticoid metabolism, and upregulating BDNF.