Persistence of abnormal neural responses to a meal in postobese individuals

Abstract

OBJECTIVE:To determine whether abnormal obese-like neural responses to a meal persist in postobese individuals, who achieved and maintained a normal body weight despite a past history of severe obesity. DESIGN AND SUBJECTS: Cross-sectional study of the brain's response to tasting and consuming a satiating meal in 11 postobese (age: 4076 y, body mass index (BMI): 23.671.9 kg/m 2 ), 23 obese (age: 2976 y, BMI: 39.673.8 kg/m 2 ) and 21 lean (age: 3379 y, BMI: 22.872.1 kg/m 2 ) subjects. MEASUREMENTS: Regional cerebral blood flow (rCBF, a marker of neural activity) at baseline (after a 36-h fast), after tasting and after consuming a satiating liquid meal was assessed using positron emission tomography and state-dependent changes (taste-baseline; satiation-baseline), and compared across groups. Subjective ratings of hunger and fullness were measured by a visual analogue scale and body fatness by dual-energy X-ray absorptiometry. RESULTS: In response to tasting the liquid meal, changes in rCBF were different in the obese as compared to the lean individuals (Po0.05, corrected for multiple comparisons) in the middle insula (peak voxel, x ¼ À41, y ¼ 1, z ¼ 8; Montreal Neurological Institute coordinates) and posterior cingulate cortex (peak voxel, x ¼ 17, y ¼ À47, z ¼ 40). The middle insular cortex exhibited a similar increase of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity did not change. In the posterior cingulate cortex, the changes in rCBF in the postobese subjects were not different from those in the other groups. In response to a satiating amount of the same liquid meal, changes in rCBF were different in the obese as compared to the lean individuals (Po0.05, corrected for multiple comparisons) in the posterior hippocampus (peak voxel, x ¼ 21, y ¼ À45, x ¼ 4), posterior cingulate cortex (peak voxel, x ¼ 17, y ¼ À47, z ¼ 40), and amygdala (peak voxel, x ¼ 27, y ¼ 1, z ¼ À24). The posterior hippocampus exhibited a similar decrease of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity increased. In the posterior cingulate cortex and amygdala, the changes in rCBF were not different between the postobese and lean individuals. None of the changes in neural activity were correlated with the age of the individuals, the subjective ratings of hunger and fullness, or the meal induced-changes in plasma glucose, insulin, or serum free fatty acids. CONCLUSION: Persistence of abnormal neural responses to a meal in the postobese individuals, a group at high risk for relapse, indicates that a predisposition to obesity may involve areas of the brain that control complex aspects of eating behavior including anticipation and reward, chemosensory perception, and autonomic control of digestion (insular cortex), as well as enteroception and learning/memory (hippocampus).

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry

“…Imaging studies have shown that the desire to eat a specific food was associated with activation of the hippocampus, which was interpreted to reflect the involvement of this region in the memories of the desired food (27). A recent study showed that tasting a liquid meal resulted in decreased activity in posterior hippocampus in obese, and previously obese but not in lean, subjects, implicating the hippocampus in the neurobiology of obesity (28). The effects of gastric stimulation on the hippocampus therefore could contribute to the decrease in food intake by interfering with the retrieval of food reward memories, decreasing saliency, and͞or strengthening inhibitory control.…”

Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing

“…For instance, amnesic patients with hippocampal damage will consume a second test meal immediately after consuming a full meal (Hebben et al, 1985;Rozin et al, 1998), which suggests that (1) they do not remember consuming the first meal and/or (2) that they are impaired in detecting and utilizing internal cues (eg meal-related gastric distension and other satiation signals) arising from the previously consumed food. Human fMRI studies show that the hippocampus is significantly activated by consuming food to satiation (DelParigi et al, 2004) as well as following gastric electrical stimulation of the vagus nerve (Wang et al, 2006) which increases subjective feelings of fullness and reduces food intake and BW in obese subjects (Cigaina, 2004). In rats, hippocampal lesions impair performance in a deprivation intensity discrimination paradigm that requires the animals to use interoceptive cues produced from different levels of food deprivation (non-deprived vs 24 h food-deprived) as discriminative cues for food reward (Davidson et al, 2010).…”

Increased dorsolateral prefrontal cortex activation in obese children during observation of food stimuli

“…28 Neuroimaging research on obesity has revealed differential patterns of neural activity in obese versus lean individuals in the orexigenic and satiation networks. These differences include a greater deactivation of limbic/paralimbic areas [28][29][30] and areas of the dopaminergic system, 24 less deactivation of the hypothalamus, 28,31 and a greater activation of prefrontal areas 28,29 in response to satiation. Others showed that obese people when observing food stimuli show even higher activations in areas associated with rewardFquite comparable to patients suffering from addictive disease.…”