Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile.
J Neuroendocrinol. 2020 Jan;32(1):e12776. doi: 10.1111/jne.12776. Epub 2019 Aug 8.
The high concentrations of free fatty acids as a consequence of obesity and being overweight have become risk factors for the development of different diseases, including neurodegenerative ailments. Free fatty acids are strongly related to inflammatory events, causing cellular and tissue alterations in the brain, including cell death, deficits in neurogenesis and gliogenesis, and cognitive decline. It has been reported that people with a high body mass index have a higher risk of suffering from Alzheimer's disease. Hormones such as oestradiol not only have beneficial effects on brain tissue, but also exert some adverse effects on peripheral tissues, including the ovary and breast. For this reason, some studies have evaluated the protective effect of oestrogen receptor (ER) agonists with more specific tissue activities, such as the neuroactive steroid tibolone. Activation of ERs positively affects the expression of pro-survival factors and cell signalling pathways, thus promoting cell survival. This review aims to discuss the relationship between lipotoxicity and the development of neurodegenerative diseases. We also elaborate on the cellular and molecular mechanisms involved in neuroprotection induced by oestrogens.
肥胖和超重导致的游离脂肪酸浓度升高，已成为多种疾病（包括神经退行性疾病）发展的风险因素。游离脂肪酸与炎症事件密切相关，导致大脑中的细胞和组织发生改变，包括细胞死亡、神经发生和神经胶质发生减少以及认知能力下降。据报道，体重指数高的人患阿尔茨海默病的风险更高。雌激素等激素不仅对脑组织有有益的影响，而且对包括卵巢和乳房在内的外周组织也有一些不利影响。出于这个原因，一些研究评估了具有更特定组织活性的雌激素受体 (ER) 激动剂的保护作用，例如神经活性甾体替勃龙。ER 的激活可积极影响促生存因子和细胞信号通路的表达，从而促进细胞存活。本文旨在讨论脂毒性与神经退行性疾病发展之间的关系。我们还详细阐述了雌激素诱导的神经保护所涉及的细胞和分子机制。
