We investigate the epigenetic connections between physiology and behavior, focusing on the role of the hypothalamus in regulating responses to thermal stress and obesity. Our research emphasizes the impact of early-life environmental conditions, aiming to uncover the intricate cross-talk among multilayered epigenetic mechanisms that fine-tune the set-point response to temperature and satiety, including its long-term effects and transgenerational transmission. By exploring how factors such as temperature and diet during critical developmental periods influence long-term hypothalamic function and metabolic outcomes, we aim to provide new insights into the regulation of energy balance, stress resilience, and metabolic health.