Laboratoire des Substances Bioactives, Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia.
Neurochem Res. 2012 Sep;37(9):2004-13. doi: 10.1007/s11064-012-0821-2. Epub 2012 Jun 9.
Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.
肥胖与痴呆风险增加有关，脂肪对大脑产生不利影响的生理机制尚不清楚。本研究分析了高脂肪饮食（HFD）对脑脂肪变性和氧化应激的影响，以及参与信号转导的细胞内介质，以及葡萄籽油和葡萄皮提取物（GSSE）提供的保护作用。HFD 诱导胆固醇和磷脂的异位沉积，但不诱导甘油三酯的异位沉积。此外，脑脂毒性与氧化应激有关，其特征是脂质过氧化和羰基化增加、谷胱甘肽过氧化物酶和超氧化物歧化酶活性抑制、锰耗竭以及可离子化钙和乙酰胆碱酯酶活性增加。重要的是，GSSE 减轻了 HFD 治疗的所有不良影响。总之，我们的数据表明，HFD 可能在锰中毒的治疗中具有一定的应用潜力，GSSE 应该作为一种安全的抗脂毒性剂，用于预防和治疗脂肪诱导的脑损伤。
