Chronic high-fat diet (HFD) consumption caused not only negative effects on obesity and metabolic disturbance, but also instigated several brain pathologies, including dendritic spine loss. In addition, alterations in plasma/brain neurotensin (NT) levels and NT signaling were observed in obesity. However, the mechanistic link between the NT levels in plasma and brain, NT signaling, and peripheral/brain pathologies following prolonged HFD consumption still needs to be elucidated. We hypothesized that an increase in peripheral/brain NT signaling were associated with peripheral/brain pathologies after prolonged HFD consumption. Male Wistar rats (n = 24) were given either a normal diet (ND) or a HFD for 12 and 40 weeks. At the end of each time course, metabolic parameters and plasma NT levels were measured. Rats were then decapitated and the brains were examined the levels of brain NT, hippocampal reactive oxygen species, the number of Iba-1 positive cells, the dendritic spine densities, and the expression of NT-, mitophagy-, autophagy-, and apoptotic-related proteins. The findings showed an increase in the level of plasma NT with dyslipidemia, metabolic disturbances, systemic inflammation/oxidative stress, and hippocampal pathologies in rats fed HFD for 12 and 40 weeks. The expression of brain NT signaling and brain apoptosis were markedly increased after 40 weeks of HFD feeding. These results indicated that the alteration in the level of circulating/brain NT and its downstream signaling were associated with central and peripheral pathologies after long-term HFD intake. Therefore, these alterations in NT level or its signaling could be considered as a therapeutic target in treating obesity.

中文翻译：

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慢性高脂肪饮食会导致血浆/脑神经降压素信号传导、代谢紊乱、全身炎症/氧化应激、脑细胞凋亡和树突棘丢失的改变

慢性高脂肪饮食 (HFD) 消费不仅对肥胖和代谢紊乱造成负面影响，而且还引发了多种脑部疾病，包括树突棘丢失。此外，在肥胖患者中观察到血浆/脑神经降压素 (NT) 水平和 NT 信号的改变。然而，血浆和大脑中 NT 水平、NT 信号传导和长期食用 HFD 后外周/大脑病理之间的机制联系仍然需要阐明。我们假设在长期使用 HFD 后外周/大脑 NT 信号的增加与外周/大脑病变有关。雄性 Wistar 大鼠 (n = 24) 被给予正常饮食 (ND) 或 HFD 12 和 40 周。在每个时间过程结束时，测量代谢参数和血浆 NT 水平。然后将大鼠斩首，并检查大脑 NT 水平、海马活性氧、Iba-1 阳性细胞数量、树突棘密度以及 NT-、线粒体自噬-、自噬-和凋亡-的表达。相关蛋白质。研究结果表明，在喂食 HFD 12 和 40 周的大鼠中，血浆 NT 水平升高，伴有血脂异常、代谢紊乱、全身炎症/氧化应激和海马病变。喂食HFD 40周后，脑NT信号和脑细胞凋亡的表达显着增加。这些结果表明，循环/大脑 NT 水平的改变及其下游信号与长期摄入 HFD 后的中枢和外周病变有关。所以，