Obesity results from an imbalance between caloric intake and energy expenditure, predominating the first over the second. Since behavioral approaches such as diets and physical activity have proved insufficient to contain the spread of this epidemiological phenomenon, it is believed that only the development of new prophylactic and therapeutic methodologies will result in better control of this disease. Since hypothalamus coordinate control of feeding and energy expenditure, it is believed that a good characterization of their functional regulation may offer new perspectives for the treatment of obesity. The consumption of dietary saturated fats promotes the activation of an inflammatory process in the hypothalamus which results in impairment of its physiological activity in the regulation of energy homeostasis. Such inflammation can induce neuronal apoptosis which plays an important role in the anomalous regulation of food intake and energy expenditure. The purpose of this study is to evaluate the effect of saturated fatty acids in autophagy induction in hypothalamic neurons and test the fatty acids involvement in the neuronal apoptosis. Autophagy is a cellular process that leads to structural substrates use for energy production. It occurs to protect the cell in risky situations like nutritional deficiency, inflammation and blood supply deficit. The cell returns to its baseline functional pattern if the noxious stimulus can be controlled, otherwise the cell evolves to apoptosis. Mice will be submitted to a protocol of diet-induced obesity and the presence and distribution of neurons in autophagy will be evaluated by transmission electron microscopy. Modulation of hypothalamic inflammation will be performed by pharmacological and genetic approaches and its impact on autophagy will be explored. We believe this study will contribute to advance in the understanding of the pathophysiological mechanisms involved in the hypothalamic dysfunction in obesity.
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