Allan Geliebter

Neuroimaging and obesity: current knowledge and future directions

Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite‐related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications.

Emotional eating in overweight, normal weight, and underweight individuals

Emotional states and situations can affect food intake. We predicted that underweight individuals would eat less and overweight individuals would eat more during negative as well as positive emotional states and situations. Questionnaires to assess eating during emotional states and situations were distributed and collected in person in several major university and public libraries. Ninety questionnaires, representing for each gender the 15 most overweight, the 15 closest to normal weight, and the 15 most underweight, were analyzed. Gender had only minor effects on the eating ratings, and therefore the results are presented for the sexes combined. Underweight individuals reported eating less (P=.000) than both the normal and overweight groups during negative emotional states and situations. More surprisingly, underweight individuals also reported eating more (P=.01) than the other groups during positive emotional states and situations. Thus, part of the prediction was confirmed: the relative undereating by the underweight group, and the relative overeating by the overweight group during negative emotional states and situations. As compared to their usual eating behavior, undereating by underweight individuals during negative emotional states and situations was of a greater magnitude than their own overeating during positive states and situations (P=.01). Undereating by underweight individuals when experiencing negative emotions may contribute to their low body weight.

Gastric distension and gastric capacity in relation to food intake in humans

Two studies were performed in the same subjects to explore the relationship between stomach capacity and food intake. In the first study, a balloon was passed orally into the stomach of four lean and four obese subjects before they ingested a liquid lunch meal. The balloon was filled with 0, 200, 400, 600, and 800 ml of water in a random sequence on different days. The balloon was kept inflated during ingestion then deflated and removed. Food intake was significantly reduced (p less than 0.01) by a balloon volume of greater than or equal to 400 ml. In the second study, another balloon was inserted into the stomach of these subjects to estimate stomach capacity. The balloon was gradually filled at the rate of 100 ml/min with 30 sec pauses. The subjects rated their discomfort as 1 to 10, from no discomfort to extreme discomfort. A rating of 10 was the main index for stomach capacity. Mean capacity (ml) for the lean subjects was 1100 +/- 185 (SE) and for the obese 1925 +/- 175 (SE), t = 3.24, p less than 0.02. When stomach capacity from the second study was correlated to spontaneous food intake at 0 balloon volume from the first study, r = .44, n.s. However, the relationship between stomach capacity and the balloon volume needed to suppress 50% of spontaneous intake was significant, r = .66, p less than 0.05. This may have implications for treatment of obesity with a gastric balloon.

Gastric distention activates satiety circuitry in the human brain.

Gastric distention during meal ingestion activates vagal afferents, which send signals from the stomach to the brain and result in the perception of fullness and satiety. Distention is one of the mechanisms that modulates food intake. We measured regional brain activation during dynamic gastric balloon distention in 18 health subjects using functional magnetic resonance imaging and the blood oxygenation level-dependent (BOLD) responses. The BOLD signal was significantly changed by both inflow and outflow changes in the balloons volume. For lower balloon volumes, water inflow was associated with activation of sensorimotor cortices and right insula. The larger volume condition additionally activated left posterior amygdala, left posterior insula and the left precuneus. The response in the left amygdala and insula was negatively associated with changes in self-reports of fullness and positively with changes in plasma ghrelin concentration, whereas those in the right amygdala and insula were negatively associated with the subjects body mass index. The widespread activation induced by gastric distention corroborates the influence of vagal afferents on cortical and subcortical brain activity. These findings provide evidence that the left amygdala and insula process interoceptive signals of fullness produced by gastric distention involved in the controls of food intake.

Proposed Diagnostic Criteria for Night Eating Syndrome

OBJECTIVE To propose criteria for diagnosis of the night eating syndrome (NES). METHOD An international research meeting was held in April 2008, and consensus criteria for NES diagnosis were determined. RESULTS The core criterion is an abnormally increased food intake in the evening and nighttime, manifested by (1) consumption of at least 25% of intake after the evening meal, and/or (2) nocturnal awakenings with ingestions at least twice per week. Awareness of the eating episodes is required, as is distress or impairment in functioning. Three of five modifiers must also be endorsed. These criteria must be met for a minimum duration of 3 months. DISCUSSION These criteria help standardize the definition of NES. Additional aspects of the nosology of NES yet to be fully elaborated include its relationship to other eating and sleep disorders. Assessment and analytic tools are needed to assess these new criteria more accurately.

Obese Patients Have Inadequate Protein Intake Related to Protein Intolerance Up to 1 Year Following Roux-en-Y Gastric Bypass

Background: Inadequate protein intake is a concern following Roux-en-Y gastric bypass (RYGBP). The small gastric pouch and bypass restrict energy intake and may lead to insufficient protein intake and absorption, and excess loss of lean tissue. Methods:We evaluated protein intake in 93 (77 F,16 M) morbidly obese individuals (BMI = 52.0±12.9 [SD]) who underwent RYGBP at our medical center. Participants completed 24-hr food recalls and received nutritional counseling at 3, 6, and 12 months following surgery. Results: Daily energy intake (kcal/day) increased from 849±329 (SD) at 3 months to 1,101±400 at 12 months (P=.009). Protein intake also increased (g/day) from 45.6±14.2 at 3 months to 58.5±17.1 at 12 months (P=.04), and as a percentage of goal protein intake from 55.1%±23.0 at 3 months to 73.5%±38.0 at 12 months (P=.02). Although energy and protein intake increased significantly over the 12-month period, protein intake at 12 months remained significantly lower (P=.01) than the daily recommended guidelines (1.5 g/kg IBW) for a low-energy restrictive diet. Energy intake did not differ in those who reported food intolerances at 3 months (P=.77) or 6 months (P=.65), but was lower in them at 12 months (trend, P=.06). Also at 12 months, protein intake (P=.02) and percentage of protein intake goal (P=.04) were significantly lower in those with protein intolerance. Conclusions: These results suggest that postoperative patients consume insufficient amounts of protein, possibly mediated by protein intolerance. Protein supplementation following RYGBP deserves further consideration.

Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [11C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food‐deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.

Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation.

Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[18F]fluoro-D-glucose (18FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are regions involved in emotional regulation, conditioning, and motivation. The suppressed activation of the orbitofrontal cortex with inhibition in men was associated with decreases in self-reports of hunger, which corroborates the involvement of this region in processing the conscious awareness of the drive to eat. This finding suggests a mechanism by which cognitive inhibition decreases the desire for food and implicates lower ability to suppress hunger in women as a contributing factor to gender differences in obesity.

Selective Reduction in Neural Responses to High Calorie Foods Following Gastric Bypass Surgery

Objective:To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity. Background:Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure. However, the mechanisms of action in RYGB are not well understood. A significant proportion of the resulting reduction in caloric intake is unaccounted for by the restrictive and malabsorptive mechanisms and is thought to be mediated by neuroendocrine function. Numerous investigations of postsurgical changes in gut peptides have resulted; however, changes in neural activation after RYGB surgery have not been previously investigated. METHODS:Functional magnetic resonance imaging and verbal rating scales were used to assess brain activation and desire to eat in response to high- and low-calorie food cues in 10 female patients 1-month pre- and post-RYGB surgery. Results:Postsurgical reductions in brain activation were found in key areas within the mesolimbic reward pathway, which were significantly more pronounced in response to food cues that were high (vs. low) in caloric density. These changes mirrored concurrent postsurgical reductions in desire to eat, which were also greater in response to food cues that were high versus low in caloric density (P = 0.007). Conclusions:Findings support the contention that RYGB surgery leads to substantial changes in neural responses to food cues encountered in the environment, provide a potential mechanism for the selective reduction in preferences for high-calorie foods, and suggest partial neural mediation of changes in caloric intake seen after RYGB surgery.

Impulsivity and test meal intake in obese binge eating women

Greater impulsivity has been observed in those with chemical (cocaine, marijuana, alcohol) and behavioral addictions (gambling, sex, shopping), as well as in individuals with personality and conduct disorders. Greater impulsivity has also been described in those with Bulimia Nervosa and attributed to aberrations in serotonin, as has eating in response to negative affect. However, less is known about the impact of impulsivity on eating behavior in obese humans in general, and in those who meet sub-clinical and full clinical criteria for Binge Eating Disorder (BED) in particular. Using a laboratory test meal paradigm, we demonstrated: (1) greater Motor Impulsivity (Barratt Impulsivity Scale (BIS) (p = 0.05) in those with BED (n = 11) as compared to those without BED (n = 11) (2) a positive correlation between BED criteria and BIS scores (p < 0.01) (3) a positive correlation between test meal duration and Zung Depression Score, and (4) a positive correlation between Motor Impulsivity and mood rated before consuming the test meal. These associations suggest potential aberrations in serotonin transmission in BED, and a possible target for pharmacotherapy of BED especially in those who are resistant to Cognitive Behavioral Therapy.