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

Abstract

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.

Keywords: brain activity; dietary carbohydrate; obesity; reward; weight loss maintenance.

FIGURE 1

Subject flow schematic. ASL, arterial spin labeling.

FIGURE 2

Adjusted model effect of diets varying in carbohydrate-to-fat ratio on preprandial blood flow in the hypothalamus and 4-h postprandial blood flow in the NAcc (primary endpoint) in adults assigned to LOW, MOD, and HIGH diets. (A, left) Preprandial rCBF in the hypothalamus differs between test diet groups (HIGH: n = 20; MOD: n = 22; LOW: n = 28), P < 0.001, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Statistical maps for rCBF are overlaid on a normalized canonical image (MNI ICBM 152 nonlinear asymmetric T1 template), with SPM color map corresponding to relative F value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) Preprandial rCBF in the hypothalamus is 41% higher in individuals assigned to the high-carbohydrate diet compared with those assigned to the low-carbohydrate diet. Bar graph depicts mean rCBF within the cluster ± SEM. Means without a common letter differ, P < 0.05, FWE-corrected. The P value reflects the post hoc comparison (independent samples t test) between HIGH and LOW groups. (B, left) Late postprandial rCBF in the NAcc differs between test diet groups (HIGH: n = 20; MOD: n = 22; LOW: n = 28), P < 0.01, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Statistical maps for the rCBF are overlaid on a normalized canonical image (MNI ICBM 152 nonlinear asymmetric T1 template), with SPM color map corresponding to relative F value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) Late postprandial rCBF in the NAcc is 43% higher in individuals assigned to the high-carbohydrate diet compared with those assigned to the low-carbohydrate diet. Bar graph depicts mean rCBF within the cluster ± SEM. Means without a common letter differ, P < 0.001, FWE-corrected. The P value reflects the post hoc comparison (independent samples t test) between HIGH and LOW groups. CBF, cerebral blood flow; FWE, family-wise error; HIGH, high-carbohydrate diet; LOW, low-carbohydrate diet; MNI, Montreal Neurologic Institute; MOD, moderate-carbohydrate diet; NAcc, nucleus accumbens; rCBF, regional cerebral blood flow; SPM, Statistical Parametric Mapping.

FIGURE 3

Adjusted model of effect of diets varying in carbohydrate-to-fat ratio on whole-brain 4-h postprandial blood flow in adults assigned to LOW, MOD, and HIGH diets. (A) Four-hour postprandial rCBF in the cerebellum differs between test diet groups (HIGH: n = 20, MOD: n = 22, LOW: n = 28), P < 0.01, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Whole-brain statistical maps based on the ANCOVA show any group differences between LOW, MOD, and HIGH groups in rCBF, overlaid on axial slices of a normalized canonical image (ch2better template), with SPM color map corresponding to relative F value. Coordinates (z) are presented in MNI space, with z values corresponding to the axial plane. (B) Four-hour postprandial rCBF in the cerebellum is higher in individuals assigned to the high-carbohydrate diet compared with those assigned to the low-carbohydrate diet, P < 0.05, FWE-corrected. The t scale and P value reflect the post hoc comparison (independent samples t test) between HIGH and LOW groups. Whole-brain statistical maps based on post hoc group comparisons show HIGH > LOW group differences in rCBF, overlaid on axial slices of a normalized canonical image (ch2better template), with SPM color map corresponding to relative t value. Coordinates (z) are presented in MNI space, with z values corresponding to the axial plane. FWE, family-wise error; HIGH, high-carbohydrate diet; LOW, low-carbohydrate diet; MNI, Montreal Neurologic Institute; MOD, moderate-carbohydrate diet; rCBF, regional cerebral blood flow; SPM, Statistical Parametric Mapping.

FIGURE 4

Adjusted model of effect of diets varying in carbohydrate-to-fat ratio on whole-brain preprandial blood flow in adults assigned to LOW, MOD, and HIGH diets. (A) Preprandial rCBF in the caudate, putamen, anterior cingulate gyrus, middle frontal gyrus, precentral gyrus, fusiform gyrus, and posterior cingulate gyrus differs between test diet groups (HIGH: n = 20; MOD: n = 22; LOW: n = 28), P < 0.01, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Whole-brain statistical maps based on the ANCOVA show any group differences in rCBF, overlaid on axial slices of a normalized canonical image (ch2better template), with SPM color map corresponding to relative F value. Coordinates (z) are presented in MNI space, with z values corresponding to the axial plane. (B) Preprandial rCBF in the pulvinar nucleus, caudate, anterior cingulate gyrus, insula, angular gyrus, and occipital gyrus is higher in individuals assigned to the high-carbohydrate diet compared with those assigned to the low-carbohydrate diet, P < 0.05, FWE-corrected. The t scale and P value reflect the post hoc comparison (independent samples t test) between HIGH and LOW groups. Whole-brain statistical maps based on post hoc group comparisons show HIGH > LOW group differences in rCBF, overlaid on axial slices of a normalized canonical image (ch2better template), with SPM color map corresponding to relative t value. Coordinates (z) are presented in MNI space, with z values corresponding to the axial plane. FWE, family-wise error; HIGH, high-carbohydrate diet; LOW, low-carbohydrate diet; MNI, Montreal Neurologic Institute; MOD, moderate-carbohydrate diet; rCBF, regional cerebral blood flow; SPM, Statistical Parametric Mapping.

FIGURE 5

Adjusted model of effect of diets varying in carbohydrate-to-fat ratio on preprandial blood flow in the nucleus accumbens and 4-h postprandial blood flow in the hypothalamus in adults assigned to LOW, MOD, and HIGH diets. (A, left) Preprandial rCBF in the NAcc differs between test diet groups (HIGH: n = 20; MOD: n = 22; LOW: n = 28), P < 0.01, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Statistical maps for the rCBF are overlaid on a normalized canonical image (MNI ICBM 152 nonlinear asymmetric T1 template), with SPM color map corresponding to relative F value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) Preprandial rCBF in the NAcc is 51% higher in individuals assigned to the high-carbohydrate diet compared with those assigned to the low-carbohydrate diet. Bar graph depicts mean rCBF within the cluster ± SEM. Means without a common letter differ, P < 0.001, FWE-corrected. The P value reflects the post hoc comparison (independent samples t test) between HIGH and LOW groups. (B, left) Late postprandial rCBF in the hypothalamus differs between test diet groups (HIGH: n = 20; MOD: n = 22; LOW: n = 28), P < 0.01, FWE-corrected. The F scale and P value reflect the 3-way (HIGH, MOD, LOW) ANCOVA. Statistical maps for the rCBF are overlaid on a normalized canonical image (MNI ICBM 152 nonlinear asymmetric T1 template), with SPM color map corresponding to relative F value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) Late postprandial rCBF in the hypothalamus is 36% higher in individuals assigned to the high-carbohydrate diet compared with those in the low-carbohydrate diet. Bar graph depicts mean rCBF within the cluster ± SEM. Means without a common letter differ, P < 0.001, FWE-corrected. The P value reflects the post hoc comparison (independent samples t test) between HIGH and LOW groups. CBF, cerebral blood flow; FWE, family-wise error; HIGH, high-carbohydrate diet; LOW, low-carbohydrate diet; MNI, Montreal Neurologic Institute; MOD, moderate-carbohydrate diet; NAcc, nucleus accumbens; rCBF, regional cerebral blood flow; SPM, Statistical Parametric Mapping.

FIGURE 6

Relation between insulin secretion and 4-h postprandial blood flow in the nucleus accumbens in adults assigned to LOW, MOD, and HIGH diets. (A, left) Pre-weight-loss insulin secretion (insulin concentration 30 min after oral glucose, obtained at the pre-weight-loss time point as part of the parent study protocol) differentially predicted late postprandial right NAcc rCBF in those assigned to the low- compared with high-carbohydrate weight-loss maintenance diets (HIGH: n = 20; LOW: n = 28), P < 0.05, FWE-corrected using small volume correction (P < 0.005, uncorrected). Statistical maps are overlaid on the MNI ICBM 152 nonlinear asymmetric T1 template, with SPM color map corresponding to relative t value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) In the low-carbohydrate group, the relation between pre-weight-loss insulin secretion and late postprandial right NAcc rCBF was positive, whereas in the high-carbohydrate group there was an inverse relation. Scatterplots depict average rCBF within the cluster plotted against insulin secretion, with correlation coefficients specified for each group. (B, left) End of diet test insulin secretion (insulin concentration 30 min after oral glucose, obtained at the 18- to 20-wk time point as part of the parent study protocol) differentially predicted late postprandial right NAcc rCBF in those assigned to the low- compared with high-carbohydrate weight-loss maintenance diets (HIGH: n = 19; LOW: n = 28), P = 0.14, FWE-corrected using small volume correction (P < 0.05, uncorrected). Statistical maps are overlaid on the MNI ICBM 152 nonlinear asymmetric T1 template, with SPM color map corresponding to relative t value. Coordinates (y, z) are presented in MNI space, with y corresponding to the coronal plane and z to the axial plane. (Right) In the low-carbohydrate group, there was a positive relation between end of diet test insulin secretion and late postprandial right NAcc rCBF. The high-carbohydrate group showed an inverse relation. Scatterplots depict average rCBF within the cluster plotted against insulin secretion, with correlation coefficients specified for each group. CBF, cerebral blood flow; FWE, family-wise error; HIGH, high-carbohydrate diet; LOW, low-carbohydrate diet; MNI, Montreal Neurologic Institute; NAcc, nucleus accumbens; rCBF, regional cerebral blood flow; SPM, Statistical Parametric Mapping.