Effects of Macronutrient Diet on Brain Activity

A question critical to the field of obesity is "what causes overweight and obese individuals to overeat?" One common explanation holds that weight gain at the population-level is caused by increases in the widespread availability of highly palatable foods. An alternative explanation is that the biological effects of the modern diet produce effects in the central nervous system and periphery that augment homeostatic and hedonic hunger. Reducing glycemic load preferentially maintains total energy expenditure during weight-loss maintenance (Ebbeling et al., 2012), and this group of investigators previously showed that in the late postprandial period, a nutrient-controlled high glycemic load vs. low glycemic load meal increases resting regional cerebral blood flow in the nucleus accumbens (Lennerz et al., 2013), part of the mesoaccumbal reward circuitry implicated in craving and addiction. However, the effects of macronutrient composition on blood flow to and activity in homeostatic and reward-related brain regions cannot be fully ascertained from studies of acute ingestion of a single macronutrient, because these do not generalize to mixed-nutrient meals consumed as part of typical American diets. Further, retrospective designs that rely on participant report of frequency of recent macronutrient ingestion and prospective designs with limited duration of diet prescription cannot address the critical question of the long-term, cumulative effects of dietary composition on brain function. Therefore, the investigators propose an approach to identifying brain responses to randomized, mixed-meal diets of varying macronutrient composition during long-term weight-loss maintenance on these diets, using arterial spin labeling (ASL) for regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD)-based functional connectivity.

To explore these outcomes, the investigators will partner with the ongoing Framingham State Food Study (NCT02068885): Following weight loss on a standard diet, 150 overweight or obese adults (aged 18 to 65 years) will be randomized to one of three weight-loss maintenance diets varying in carbohydrate to fat ratios for 20 weeks. Investigators will invite subjects already enrolled in the Framingham State Food Study to participate with a goal of enrolling 75 subjects (aiming to be equally divided per diet group following randomization to assigned test diet in the parent study). Participants will complete 1 morning visit to the MRI imaging center at Brigham and Women's Hospital approximately 14-20 weeks into the weight maintenance test diet phase. During the visit, they will undergo a fasting baseline brain imaging session, consume their assigned diet breakfast meal, and undergo a late postprandial brain imaging session. Participants will additionally provide frequent ratings of their food cravings, mood, and anxiety level throughout the visit. The main outcomes will be resting blood flow to the nucleus accumbens and connected striatal regions in the late postprandial period, with additional secondary and other outcomes including blood flow to the hypothalamus and connectivity between the hypothalamus during the late postprandial period.