Effect of intermittent fasting on UPRmt in the hypothalamus of obese mice

Abstract

Mitochondrial metabolism in specific subpopulations of hypothalamic neurons plays a critical role in the control of food intake and energy homeostasis. Excessive consumption of diets high in saturated fats can trigger deleterious signals to hypothalamic neurons, including neuroinflammation, oxidative stress, and reduced mitochondrial activity. Under cellular stress conditions, mitochondria are protected by different mechanisms aimed at maintaining or restoring proteostasis and mitochondrial activity. Among these mechanisms, the UPRmt (Unfolded Protein Response) stands out. Interestingly, intermittent fasting and caloric restriction are known to induce metabolic stress that lead to a positive adaptation of both morphology and mitochondrial activity, and both have been widely used to prevent or treat Obesity. However, the effects of intermittent fasting on mitochondrial metabolism, and in particular UPRmt in hypothalamic neurons, are completely unknown. Thus, the aim of this project is to investigate the effect of intermittent fasting on the UPRmt in the hypothalamus of obese rodents. Analyzes of dissection of the hypothalamic nuclei, immunofluorescence, gene editing using siRNA in cell culture, assessment of mitochondrial respiration, bioinformatics analysis, among others, will be combined. We are certain that the development of this project will contribute to the advancement of knowledge about the effects of fasting on UPRmt in populations of hypothalamic neurons, as well as the relationship of this mechanism on the development of the obese phenotype. (AU)