Diet-induced changes in the Lean Brain: Hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region

Abstract

It is evident that there is a relationship between the brain's serotonin system and obesity. Although it is clear that drugs affecting the serotonin system regulate appetite and food intake, it is unclear whether changes in the serotonin system are cause or consequence of obesity. To determine whether obesogenic eating habits result in reduced serotonin transporter (SERT)-binding in the human hypothalamic region, we included 25 lean, male subjects who followed a 6-week-hypercaloric diet, which were high-fat-high-sugar (HFHS) or high-sugar (HS) with increased meal size or -frequency (=snacking pattern). We measured SERT-binding in the hypothalamic region with SPECT. All hypercaloric diets significantly increased body weight by 3-3.5%. Although there were no differences in total calories consumed between the diets, only a hypercaloric HFHS-snacking diet decreased SERT-binding significantly by 30%. We here show for the first time in humans that snacking may change the serotonergic system increasing the risk to develop obesity.

Keywords: Fat; Human imaging; Hypercaloric diet; Meal pattern; Serotonin transporters; Sugar.

Figure 1

Randomisation flowchart. Number of subjects initially included and randomised; drop-out and reason for drop-out and final number of subjects on which data analysis was performed. HFHS=high-fat-high-sugar; HS=high-sugar. S=increased meal size; F=increased meal frequency.

Figure 2

Body weight gain and food intake. HFHS=high-fat-high-sugar; HS=high-sugar. S=increased meal size; F=increased meal frequency.(A) All hypercaloric diet groups showed significantly increased body weight compared to the control group. There were no differences in body weight gain between the hypercaloric diet groups (data are depicted in mean ±SEM; *p<0.01). (B) Caloric intake in kCal/day during the intervention period: Ad libitum intake is depicted in light grey and added HFHS or HS calories are depicted in dark grey. Total intake, and also ad lib and diet intake were similar in all hypercaloric diet groups, whereas intake for all hypercaloric diet groups were increased compared to the control group (data depicted as mean±±SEM; ***p<0.0001). (C) Carbohydrate- and fat intake in kCal/day during the intervention period displayed as mean and SEM. Subjects on HFHS consumed more fat and carbohydrate calories compared to the controls, whereas subject on HS consumed more carbohydrate calories, but equal fat calories, compared to controls. No significant differences were detected between HFHS-S and HFHS-F, and between HS-S and HS-F (data depicted as mean±±SEM; ***p<0.0001).

Figure 3

SERT binding. HFHS=high-fat-high-sugar; HS=high-sugar. S=increased meal size; F=increased meal frequency. (A) SERT binding activity in diencephalon in the 4 hypercaloric diet groups displayed as % change. A hypercaloric diet with surplus calories in between the meals (frequency) showed lower SERT binding activity compared to hypercaloric diet with the surplus given with the meals (size) (overall effect of meal pattern (freq vs. size): p=0.01). (B) SERT binding activity decreased 30% after 6 weeks in a HFHS-F diet (paired t-test”: **p=0.004). There was no significant change in SERT binding activity in the other diet groups or the control group (not shown).