We recently demonstrated that participants engaged in an intensive intervention employing caloric restriction and vigorous exercise had a profound slowing of metabolism that was significantly greater than expected due to weight loss alone. This phenomenon is called metabolic adaptation and has also been observed following weight loss through caloric restriction without exercise and may persist long after weight loss has ceased. Metabolic adaptation has been hypothesized to limit weight loss and predispose individuals to weight regain, but this has yet to be demonstrated and the concept is controversial. In addition to the metabolic adaptations to weight loss, the brain also adapts in ways that enhance the activation of reward regions in response to palatable food cues and their receipt. In particular, the brain s dopamine circuitry is believed to be altered in obesity and it is presently unclear how this pathway responds to a weight loss intervention in humans.