High-calorie diets can lead to liver fat accumulation and disrupt brain insulin action in healthy-weight men, even in a short period, without significant changes in body weight or peripheral insulin sensitivity. Brain insulin responsiveness can adapt to short-term dietary changes before weight gain occurs, potentially contributing to the development of obesity and associated diseases. Brain changes persisted after the cessation of the high-caloric diet, indicating prolonged effects on the brain that outlast the time frame of dietary consumption.