EXPLORING HYPOTHALAMIC NEUROGENESIS: NOVEL INSIGHTS INTO BODY WEIGHT REGULATION

Obesity is a major public health challenge due to its increasing prevalence and associated metabolic complications. Despite progress achieved through dietary interventions, physical activity, and pharmacological treatments that yield encouraging short-term effects, weight regain is almost inevitable. This limited long-term efficacy highlights the need for a better understanding of the central mechanisms regulating energy balance, and how they are affected by chronic obesity. Among the brain structures involved, the hypothalamus plays a key role by integrating metabolic and hormonal signals to adjust food intake and energy expenditure. Recent studies suggest that adult neurogenesis occurs within the hypothalamus, contributing to context-dependent remodeling of neuronal circuits, thus influencing body weight regulation. However, the origin, identity, and precise function of these newly generated neurons remain poorly understood. This project aims to characterize adult hypothalamic neurogenesis and to define its impact on energy balance. Using an innovative transgenic mouse model combined with fluorescent labeling, we track the differentiation of progenitor cells into neurons while overcoming limitations of previous models. We also investigate how different metabolic contexts, including diet, physical activity, and biological sex, modulate this neurogenic process. Our preliminary findings indicate that specific metabolic conditions significantly influence the generation of new hypothalamic neurons. A second experimental phase is currently underway to validate a complementary model allowing selective manipulation of these neurons (pharmacological activation via stereotaxic surgery), combined with real-time metabolic analysis. By exploring hypothalamic neuronal plasticity and its role in energy balance regulation, this study may contribute to the development of durable therapeutic strategies.