Metabolic disease is a major global health challenge. In humans, obesity and insulin resistance are associated with fatty liver disease and type 2 diabetes and are often difficult to reverse. Yet in nature, some animals routinely enter and exit similar metabolic states without harm. Mouse lemurs are small, short-lived primates that survive dramatic seasonal changes in food availability by naturally shifting their metabolism. In early winter, they gain up to 50% of their body weight to store energy. Later in the season, they become temporarily insulin resistant and slow their metabolism to conserve fuel for vital organs like the brain. Although seasonal physiological changes are well characterized, we still do not understand how mouse lemurs safely switch between these metabolic states at the cellular and tissue level. Our research will integrate advanced genetic and biochemical tools to uncover the specific biological programs that allow mouse lemurs to adapt to seasonal changes. Deciphering these molecular mechanisms may reveal fundamental principles of metabolic resilience that nominate therapeutic targets for obesity, fatty liver disease, and diabetes. Importantly, as a primate, the mouse lemur offers a model in which these mechanisms are likely to be more translationally relevant. More broadly, this work will deepen our understanding of how metabolic genes coordinate responses to environmental and hormonal signals to maintain health.