Losing weight can be life saving for people with obesity. However, among patients that do lose significant weight, most have trouble keeping the weight off. Both the obese state and the post-obesity weight loss state are associated with physiological, behavioral, and neural changes that defend the elevated body weight, including decreases in metabolic rate and increases in appetite. These changes resemble adaptive mechanisms that defend body weight during periods of food scarcity, but for people trying to achieve a healthy body weight and stay there, these mechanisms are decidedly maladaptive. In this talk, I will discuss recent research from our lab looking at neural circuits that modulate food appetite, and how these circuits change as mice become obese and then lose weight. We employ both in vivo and ex vivo circuit analysis to measure the activity of D1-receptor and D2-receptor expressing neurons (D1SPNs and D2SPNs, respectively) in the nucleus accumbens, observing that activity in D1SPNs was enhanced in obese mice, and that their activity during food seeking grew even stronger following weight loss. These enhancements in activity were not observed in D2SPNs, suggesting that obesity selectively engages D1SPNs in the nucleus accumbens. In a final set of experiments we found that blocking synaptic output from D1SPNs, but not D2SPNs, attenuated the development of diet-induced obesity, establishing the necessity of D1SPNs in the development of obesity.