Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults.

BACKGROUND: Obesity has one of the highest refractory rates of all chronic diseases, in part because weight loss induced by calorie restriction, the first-line treatment for obesity, elicits biological adaptations that promote weight regain. Although acute feeding trials suggest a role for macronutrient composition in modifying brain activity related to hunger and satiety, relevance of these findings to weight-loss maintenance has not been studied. OBJECTIVES: We investigated effects of weight-loss maintenance diets varying in macronutrient content on regional cerebral blood flow (rCBF) in brain regions involved in hunger and reward. METHODS: In conjunction with a randomized controlled feeding trial, we investigated the effects of weight-loss maintenance diets varying in carbohydrate content [high, 60% of total energy: n = 20; 6 men/14 women; mean age: 32.5 y; mean BMI (in kg/m 2): 27.4; moderate, 40% of total energy: n = 22; 10 men/12 women; mean age: 32.5 y; mean BMI: 29.0; low, 20% of total energy: n = 28; 12 men/16 women; mean age: 33.2 y; mean BMI: 27.7] on rCBF in brain regions involved in hunger and reward preprandial and 4 h postprandial after 14-20 wk on the diets. The primary outcome was rCBF in the nucleus accumbens (NAcc) at 4 h postprandial; the secondary outcome was preprandial rCBF in the hypothalamus. RESULTS: Consistent with a priori hypothesis, at 4 h postprandial, NAcc rCBF was 43% higher in adults assigned to the high- compared with low-carbohydrate diet {P[family-wise error (FWE)-corrected] < 0.05}. Preprandial hypothalamus rCBF was 41% higher on high-carbohydrate diet [P(FWE-corrected) < 0.001]. Exploratory analyses revealed that elevated rCBF on high-carbohydrate diet was not specific to prandial state: preprandial NAcc rCBF [P(FWE-corrected) < 0.001] and 4 h postprandial rCBF in hypothalamus [P(FWE-corrected) < 0.001]. Insulin secretion predicted differential postprandial activation of the NAcc by diet. CONCLUSIONS: We report significant differences in rCBF in adults assigned to diets varying in carbohydrate content for several months, which appear to be partially associated with insulin secretion. These findings suggest that chronic intake of a high-carbohydrate diet may affect brain reward and homeostatic activity in ways that could impede weight-loss maintenance. This trial was registered at clinicaltrials.gov as NCT02300857.

Divergent associations between ghrelin and neural responsivity to palatable food in hyperphagic and hypophagic depression.

BACKGROUND: The neurobiological mechanisms involved in divergent appetitive phenotypes in major depressive disorder (MDD) are not well understood, although recent data suggest disruption in mesolimbic reward circuitry. Ghrelin, an orexigenic hormone, has been shown to modulate the reward circuitry. We aimed to investigate the relationship between acylated ghrelin levels and the neural response to food stimuli in individuals with hyperphagic and hypophagic MDD in remission. METHODS: Women with hyperphagic MDD (n = 10), hypophagic MDD (n = 18), and healthy controls (HC; n = 18) underwent fMRI scanning during which they viewed images of food. The fMRI session was followed by a standardized meal, appetite ratings, and serial blood draws. RESULTS: In individuals with hyperphagic MDD, greater change in acylated ghrelin in response to a meal was associated with increased BOLD response to high-calorie food in the bilateral ventral tegmental area and left hypothalamus. In contrast, negative associations were observed between acylated ghrelin AUC and BOLD activity in the right hypothalamus in the hypophagic MDD group. LIMITATIONS: Unbalanced group sizes with a relatively small sample in the hyperphagic MDD group. CONCLUSIONS: In the absence of differences in absolute ghrelin levels between the hyperphagic MDD and HC groups, results in hyperphagic MDD might suggest a ghrelinergic signaling mechanism for increased appetite during an MDD episode in this group. Our findings shed light on interactions between appetite hormones and mesolimbic circuitry which could contribute to development of therapeutic targets for opposing appetite phenotypes in depression.

Resting-State Brain Connectivity Predicts Weight Loss and Cognitive Control of Eating Behavior After Vertical Sleeve Gastrectomy.

OBJECTIVE: The effects of sleeve gastrectomy (SG) on functional connectivity (FC) and associations with weight loss and eating-related cognitive control were investigated. METHODS: In a longitudinal study, 14 SG patients (13 female; 42.1 presurgery BMI) completed study visits 1 month pre surgery and 12 months post surgery. Patients completed the Dutch Eating Behavior Questionnaire and resting-state functional magnetic resonance imaging scanning to measure FC. Data were analyzed using a seed-to-voxel approach in the CONN Toolbox to investigate pre-/postsurgery changes (n = 12) and to conduct predictive analysis (n = 14). RESULTS: Seed-to-voxel analysis revealed changes in magnitude (decreases) and directionality (positively correlated to anticorrelated) of FC pre to post surgery within and between default mode network, salience network, and frontoparietal network nodes [Family-Wise Error (FWE) corrected at P < 0.05]. Baseline FC of the nucleus accumbens (with insula) and hypothalamus (with precentral gyrus) predicted 12-month post-SG % total weight loss (FWE-P < 0.05). Baseline FC of the hippocampus, frontoparietal network, and default mode network nodes predicted improvement in cognitive control of eating behavior 12 months after SG (FWE-P < 0.05). CONCLUSIONS: Our findings demonstrate changes in FC magnitude and directionality post versus pre surgery within and between resting-state networks and frontal, paralimbic, and visual areas in SG patients. Baseline FC predicted weight loss and changes in cognitive control of food intake behavior at 12 months. These could serve as predictive biomarkers for bariatric surgery.