Brain regulation of appetite in twins

Abstract

Background: Neural responses to highly energetic food cues are robust and are suppressed by eating. It is not known if neural responsiveness to food cues is an inherited trait and possibly even one that mediates the genetic influences on body weight that have been previously observed.

Objective: We investigated the inherited influence on brain responses to high-calorie visual food cues before and after a meal.

Design: With the use of a monozygotic twin study design, 21 healthy monozygotic twin pairs consumed a standardized breakfast and, 3.5 h later, underwent the first of 2 functional MRI (fMRI) scans with the use of visual food cues. After the first fMRI session, twins consumed a standardized meal, which was followed by the second fMRI. Serial ratings of appetite and food appeal were obtained. An ad libitum buffet was used to measure total caloric and macronutrient intakes. Intraclass correlations (ICCs) were used to test for inherited influences by comparing whether intrapair similarity was greater than interpair similarity.

Results: Body mass index was highly correlated within twin pairs (ICC: 0.96; P < 0.0001). ICCs also showed a strong intrapair similarity for the meal-induced change in hunger (ICC: 0.41; P = 0.03), fullness (ICC: 0.39; P = 0.04), and the appeal of fattening food (ICC: 0.57; P < 0.001). Twins ate a similar number of kilocalories at the buffet (ICC: 0.43; P = 0.02). Before the meal, the global brain activation across regions involved in satiety processing was not more similar in twins than in unrelated individuals. However, significant ICCs were present after the meal (ICC: 0.39; P = 0.04) and for the meal-induced change in activation by high-calorie visual food cues (ICC: 0.52; P < 0.01).

Conclusion: Inherited factors influence both satiety perception and the effect of a meal to alter regional brain responses to images of highly energetic food. This trial was registered at clinicaltrials.gov as NCT02483663.

Keywords: fMRI; food intake; obesity; satiety; visual food cues.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

Study protocol. Twin pairs completed the study visit on the same day with twin 1 receiving breakfast at 0800, and twin 2 receiving breakfast at 0830. A DXA scan was used to measure body composition. VAS appetite ratings were completed throughout the study day, and appeal ratings were done after each fMRI session. A standardized breakfast and standardized meal were given to each participant and were titrated to represent 10% and 20% of the estimated daily caloric need of participants. After the last fMRI session, participants were presented with an ad libitum buffet. DXA, dual-energy X-ray absorptiometry; fMRI, functional MRI; VAS, visual analog scale.

FIGURE 2

Inherited influences on adiposity. BMI (A) and total body fat mass (B) were highly correlated in twin pairs. Total fat mass was measured with the use of dual-energy X-ray absorptiometry. n = 21 twin pairs. Lines represents 100% within-pair agreement (i.e., the closer the data point is to the line, the more similar the twins were to each other). P values were calculated with the use of linear mixed models, and models were adjusted for sex. ICC, intraclass correlation.

FIGURE 3

Meal-induced changes in subjective satiety and appeal ratings. All study meals (arrows) induced a significant reduction in mean ± SEM hunger ratings (A) and an increase in mean ± SEM fullness ratings (B). The standardized meal (administered at T = 240 min) reduced subjective hunger (C) and increased fullness (D) more similarly between twins than in unrelated individuals. Postprandial changes in the appeal of fattening (E) and nonfattening (F) foods were also more similar in twin pairs than in unrelated individuals. Models were adjusted for sex and included 20 pairs and one individual twin who had missing data for the co-twin (i.e., the unpaired individual only contributed to the between-pair variance). P values for panels A and B (n = 41 individuals) were determined with the use of a generalized estimating equation regression. In panels C–F (n = 20 twin pairs), lines represent 100% within-pair agreement, and P values were calculated with the use of linear mixed models. *P < 0.0001. ICC, intraclass correlation; VAS, visual analog scale.

FIGURE 4

Inherited influences on food intake. Mean ± SEM ad libitum buffet intake did not differ on the basis of BMI (A) or sex (B). Standardized meals are indicated with hash marks in panels A and B. Significant ICCs were shown for total kilocalories consumed (C) and for the proportion of calculated daily needs consumed (D) at the ad libitum buffet. Twins did not consume a similar amount of calories from fat (E) at the buffet but did show trends for consuming a similar percentage of calories from carbohydrates (F) and protein (G). Daily caloric needs were estimated with the use of the Mifflin-St. Jeor equation and an activity factor. Models were adjusted for sex and included 20 pairs and one individual twin who had missing data for the co-twin (i.e., the unpaired individual only contributed to the between-pair variance). P values for panels A and B (n = 41 individuals) were determined with the use of a generalized estimating equation regression. In panels C–G (n = 20 twin pairs), lines represent 100% within-pair agreement, and P values were calculated with the use of linear mixed models. ICC, intraclass correlation.

FIGURE 5

Inherited influences on satiety as assessed by brain activation to fattening food cues before (A) and after (B) a standardized meal. Global average brain activation within satiety-related regions (Supplemental Figure 2) was not more similar within twin pairs before the standardized meal (A). After the meal, brain activation to fattening food cues was significantly more similar between twins than in unrelated individuals (B). Twins were also significantly more similar in their changes in brain activation (postmeal minus premeal values) elicited by a standardized meal than were unrelated individuals (C). n = 18 twin pairs. Lines represent 100% within-pair agreement. Models were adjusted for sex and included 18 pairs and 3 individual twins missing data for their co-twin (i.e., unpaired individuals only contributed to the between-pair variance). P values were calculated with the use of linear mixed models. ICC, intraclass correlation.

FIGURE 6

Region-by-region analysis of inherited influences on meal-induced changes in brain activation. Significant ICCs were present for changes in brain activation to fattening compared with nonfattening visual food cues in the right amygdala (A), right dorsal striatum (B), medial orbital frontal cortex (C), and ventral tegmental area (D). n = 18 twin pairs. Lines represent 100% within-pair agreement. Models were adjusted for sex and included 18 pairs and 3 individual twins who were missing data for their co-twins (i.e., unpaired individuals only contributed to the between-pair variance). P values were calculated with the use of linear mixed models. ICC, intraclass correlation.