EVALUATION OF HYPOTHALAMIC MICROGLIAL BDNF EXPRESSION MODULATED BY ACUTE EXPOSURE TO A HIGH-FAT DIET

Obesity is a chronic non-communicable disease associated with many complications, such as type 2 diabetes mellitus, cardiovascular diseases, increased mortality, among several others. It depends on a positive energy balance, caused by excessive ingestion of calories as in high-fat diets. The arcuate nucleus in the hypothalamus controls food intake and energy expenditure through POMC and AgRP neurons that perceive signals from the periphery, such as nutrients and hormones. The literature shows that increased consumption of high-fat foods produces proinflammatory cytokines – TNF-α, IL-1β, and IL-6 for example - that promote apoptosis of hypothalamic neurons, especially POMC cells. This process is mediated by microglial cells recruited by the inflammatory signaling. In addition, the composition of the diet impacts neurogenesis of the central nervous system, contributing to the worsening of the energy imbalance. The brain-derived neurotrophic factor (BDNF) is expressed by the microglia and is responsible for neuronal proliferation and survival. However, high-fat diets reduce BDNF levels. Studies about diet-induced obesity in mice showed that decreased expression of BDNF in microglia is associated with learning and memory deficits. A recent study demonstrated that fractalkine, a CX3CR1 receptor-binding protein expressed only by microglia in the brain, reduced food intake through BDNF signaling. Thus, the expression of BDNF by microglia has a significant role in the consequences of excessive consumption of fats.