For many people, obesity is largely a behavioral problem. Studies in my laboratory examine energetic “thriftiness” and their underlying genetic basis. Throughout evolution, our ancestors lived in environments of limited food. We are genetically hardwired to be thrifty in our behaviors: acquiring food when it is readily available and conserving energy (e.g. limited physical activity whenever possible). However, for humans living in a world with abundance of energy-rich foods, such thriftiness makes us susceptible to positive energy balance and obesity. Finding such root of the problem is essential for understanding and treating obesity. Our goal is to find such “thrifty” genes. We have designed novel semi-natural environments to examine “thriftiness” behavioral traits, taking advantage of microeconomic analysis of feeding behavior, combining mouse genetics and fly genetics. Fly genetics allows us to quickly search for genes that confer such traits while mouse genetics provides the relevance to human conditions. For example, we have found in fruit flies that a low level of dopamine, a brain chemical signal important for reward, confers “thriftiness” traits. We have confirmed that in mice. Conversely, elevated dopamine could be protective against obesity in mice.