Weight loss diets often target restriction of dietary fat or carbohydrate, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on human brain are unclear. We investigated whether selective isocaloric reductions in dietary fat or carbohydrate altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain reward regions in response to visual food cues in 17 inpatient adults with obesity as compared to a eucaloric baseline diet. On the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain reward regions. After the reduced fat diet,ad libitumintake shifted towards foods high in both fat and carbohydrates. These results suggest that dietary fat restriction increases tonic dopamine in brain reward regions and affects food choice in ways that may hamper diet adherence.