Effects of Macronutrient Diet on Brain Activity
Condition: Obesity
Study type: Interventional

Summary: 
      This study will evaluate the effect of macronutrient diets on brain activity in homeostatic
      and mesolimbic reward regions.
    

Detailed description: 
      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.
    

Intervention name(s): Low carbohydrate diet; Moderate carbohydrate diet; High carbohydrate diet
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein; Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein; Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science