Discussion
weight gain, eating behavior
CAVITY
We previously showed that the RC diet led to widespread metabolic and endocrine changes compared with the eucaloric baseline diet, including increased fat oxidation as well as decreased energy expenditure and decreased daily insulin secretion, whereas the RF diet did not lead to substantial peripheral metabolic or endocrine changes (The most likely interpretation of our data is that the RF diet increased striatal tonic dopamine. This would explain the observed decrease in D2BP because increased endogenous dopamine would be expected to displace the [D2 receptors are located both postsynaptically on nondopaminergic cells within the striatum and presynaptically on cell bodies, axons, and axon terminals of dopaminergic projection neurons (It is unlikely that the observed reduction in D2BP during the RF diet was due to decreased D2-like receptor density because neither dopamine depletion over 2–5 days (An increase in tonic dopamine during the RF diet occurred in conjunction with an increased selection of high-fat, high-carbohydrate foods observed during the subsequent exploratory ad libitum period. Elevations in tonic dopamine alter the balance with phasic dopamine responses (At first glance, our observation that a reduction in BOLD response to food cues during the RF diet occurred alongside a subsequent shift in ad libitum food selections toward high-fat, high-carbohydrate foods appears at odds with the literature on food cue reactivity suggesting a moderate positive association with subsequent weight gain and eating behavior (How could reduction of dietary fat result in increased tonic dopamine in the brain? Dietary fat is detected and signaled to the brain throughout the alimentary canal from taste bud cells in the oral cavity to enteroendocrine and enterocyte cells in the gut (Another potential mechanism for increased brain dopamine during the RF diet involves decreased postprandial plasma triglycerides that peak several hours after a meal in proportion to the amount of fat consumed (Why did the RC diet have no significant effect on brain D2BP or neural activity in response to food cues, as compared with baseline? We found this result surprising particularly because the RC diet significantly decreased daily insulin secretion (How might changes in brain dopamine in response to different diets relate more generally to body weight regulation? Recent mouse data suggest that the effects of brain dopamine may not be isolated to canonical hedonic pathways of food reward. For example, striatal dopamine can also influence downstream hypothalamic nuclei traditionally attributed to control homeostatic feeding and regulate body weight (