Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents

Abstract

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain.

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen‐level dependent response to glucose ingestion

“…18 In the current small study, neither group showed significant modification in hypothalamic BOLD signal after glucose ingestion. This is consistent with a study including lean adolescents (N = 14) that demonstrated no change in hypothalamic perfusion after glucose ingestion 31 ; however, the same study reported increased perfusion in adolescents with obesity (N = 24). 31 In agreement with the latter, an increase in hypothalamic BOLD signal after glucose ingestion has also been described in a study with adults with obesity and lean subjects (total N = 21), 20 and two studies involving only normal-weight adults 18,32 (N = 18 and 7, respectively).…”

From biology to behavior: a cross‐disciplinary seminar series surrounding added sugar and low‐calorie sweetener consumption

“…Rodents also develop symptoms suggesting anxiety, stress, and withdrawal symptoms when sugar is removed and exhibit potentially harmful behaviours, such as crossing a shock grid, to regain access . An altered brain response to drinking glucose and fructose has also been reported in children with obesity . Despite convincing evidence presented, Dr. Avena addressed several common critiques challenging the concept of sugar addiction (Table ) .…”

Is Sugar Addictive?

“…In the binge eaters, naloxone reduced the preference for sweet taste and the actual amounts consumed. The findings of Jastreboff et al (9) that glucose and fructose stimulate the striatal system more in the adolescents with obesity than in lean individuals indicate that these molecules have addictive or habituating potential. In many cases sucrose is consumed in sugar-sweetened beverages that also contain caffeine, a drug that stimulates the central nervous system.…”

“…The study by Jastreboff et al (9) describes functional differences in the central nervous system during response to fructose or glucose solutions. First, the executive center in the prefrontal cortex is inhibited in the obese, confirming earlier work in adolescents (11,12) and adults where Volkow et al (13) showed a significant negative correlation between BMI and metabolic activity in prefrontal cortex and cingulate gyrus.…”

“…First, the executive center in the prefrontal cortex is inhibited in the obese, confirming earlier work in adolescents (11,12) and adults where Volkow et al (13) showed a significant negative correlation between BMI and metabolic activity in prefrontal cortex and cingulate gyrus. Using leptin as a surrogate for fatness, Jastreboff et al (9) found that it was inversely related to blood flow in the prefrontal cortex. Second, the hypothalamus, which plays a key role in the homeostatic regulation of food intake, is activated by glucose/fructose in the adolescents with obesity but not in the lean, a change that might stimulate feeding in those with obesity.…”