LAV, Laboratory of Cell Signaling, University of Campinas, Campinas, SP, 13084-970, Brazil.
Faculty of Nursing, University of Campinas, Campinas, SP, 13084-970, Brazil.
J Neuroinflammation. 2018 Jan 9;15(1):10. doi: 10.1186/s12974-017-1046-8.
The consumption of large amounts of dietary fats activates an inflammatory response in the hypothalamus, damaging key neurons involved in the regulation of caloric intake and energy expenditure. It is currently unknown why the mediobasal hypothalamus is the main target of diet-induced brain inflammation. We hypothesized that dietary fats can damage the median eminence blood/spinal fluid interface.
Swiss mice were fed on a high-fat diet, and molecular and structural studies were performed employing real-time PCR, immunoblot, immunofluorescence, transmission electron microscopy, and metabolic measurements.
The consumption of a high fat diet was sufficient to increase the expression of inflammatory cytokines and brain-derived neurotrophic factor in the median eminence, preceding changes in other circumventricular regions. In addition, it led to an early loss of the structural organization of the median eminence β1-tanycytes. This was accompanied by an increase in the hypothalamic expression of brain-derived neurotrophic factor. The immunoneutralization of brain-derived neurotrophic factor worsened diet-induced functional damage of the median eminence blood/spinal fluid interface, increased diet-induced hypothalamic inflammation, and increased body mass gain.
The median eminence/spinal fluid interface is affected at the functional and structural levels early after introduction of a high-fat diet. Brain-derived neurotrophic factor provides an early protection against damage, which is lost upon a persisting consumption of large amounts of dietary fats.
大量膳食脂肪的摄入会在下丘脑引发炎症反应，破坏参与调节热量摄入和能量消耗的关键神经元。目前尚不清楚为什么中脑腹侧下丘脑是饮食引起的大脑炎症的主要靶点。我们假设膳食脂肪可以破坏正中隆起血/脑脊液界面。
用高脂肪饮食喂养瑞士小鼠，并进行实时 PCR、免疫印迹、免疫荧光、透射电子显微镜和代谢测量等分子和结构研究。
摄入高脂肪饮食足以增加正中隆起处炎症细胞因子和脑源性神经营养因子的表达，早于其他室周区的变化。此外，它导致正中隆起β1-室管膜细胞的结构组织早期丧失。这伴随着下丘脑脑源性神经营养因子表达的增加。脑源性神经营养因子的免疫中和作用恶化了正中隆起血/脑脊液界面的饮食诱导性功能损伤，增加了饮食诱导的下丘脑炎症，并增加了体重增加。
高脂肪饮食摄入后，正中隆起/脑脊液界面在功能和结构水平上早期受到影响。脑源性神经营养因子提供了对损伤的早期保护，但在持续大量摄入膳食脂肪后会失去保护。
