Effects of chronic high calorie diet on mediobasal hypothalamic satiety neuron function

Over the past three decades, the prevalence of obesity has increased, characterized by chronic high calorie intake and the accumulation of excess calories as fat tissue. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in generating feelings of satiety. Chronic consumption of high-fat foods is known to reduce neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. However, the adaptations on morphological structure, electrophysiologic properties, and the role of energy metabolism of POMC neurons under exposure to chronic high-fat diets, and whether the effects are permanent, have not been understood. This thesis aimed to investigate the adaptations of ARC-POMC neurons in mouse models exposed to a chronic high-fat diet. While POMC neuronal projections did not change in the 6-month high fat diet-exposed mice, POMC neurons developed electrophysiological irreversible resistance to leptin. Moreover, POMC activation increased consumption of high-fat diet. The only adaptation observed upon switching to a standard diet was the restoration of the role of revealing satiety in homeostatic eating behavior.