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Obesity can result from excess intake in response to environmental food cues, and stress can drive greater intake and body weight. We used a novel fMRI task to explore how obesity and stress influenced appetitive responses to relatively minimal food cues (words representing food items, presented similarly to a chalkboard menu). Twenty-nine adults (16F, 13M), 17 of whom had obesity and 12 of whom were lean, completed two fMRI scans, one following a combined social and physiological stressor and the other following a control task. A food word reactivity task assessed subjective food approach (wanting) as well as food avoidant (restraint) responses, along with neural responses, to words denoting high energy-density (ED) foods, low-ED foods, and non-foods. A multi-item ad-libitum meal followed each scan. The obese and lean groups demonstrated differences as well as similarities in activation of appetitive and attention/self-regulation systems in response to food vs. non-food, and to high-ED vs. low-ED food words. Patterns of activation were largely similar across stress and non-stress conditions, with some evidence for differences between conditions within both obese and lean groups. The obese group ate more than the lean group in both conditions. Our results suggest that neural responses to minimal food cues in stressed and non-stressed states may contribute to excess consumption and adiposity., Competing Interests: The authors have declared that no competing interests exist.

The dopamine receptor 4 (DRD4) in the prefrontal cortex (PFC) acts to modulate behaviours including cognitive control and motivation, and has been implicated in behavioral inhibition and responsivity to food cues. Adolescence is a sensitive period for the development of habitual eating behaviors and obesity risk, with potential mediation by development of the PFC. We previously found that genetic variations influencing DRD4 function or expression were associated with measures of laboratory and real-world eating behavior in girls and boys. Here we investigated brain responses to high energy-density (ED) and low-ED food cues using an fMRI task conducted in the satiated state. We used the gene-based association method PrediXcan to estimate tissue-specific DRD4 gene expression in prefrontal brain areas from individual genotypes. Among girls, those with lower vs. higher predicted prefrontal DRD4 expression showed lesser activation to high-ED and low-ED vs. non-food cues in a distributed network of regions implicated in attention and sensorimotor processing including middle frontal gyrus, and lesser activation to low-ED vs non-food cues in key regions implicated in valuation including orbitofrontal cortex and ventromedial PFC. In contrast, males with lower vs. higher predicted prefrontal DRD4 expression showed minimal differences in food cue response, namely relatively greater activation to high-ED and low-ED vs. non-food cues in the inferior parietal lobule. Our data suggest sex-specific effects of prefrontal DRD4 on brain food responsiveness in adolescence, with modulation of distributed regions relevant to cognitive control and motivation observable in female adolescents., (© 2021. The Author(s).)

Background: Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery., Methods: Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery., Results: RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery., Conclusion: Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.

Taste sensitivity and liking drive food choices and ingestive behaviors from childhood to adulthood, yet their longitudinal association with dietary intake and BMI is largely understudied. Here, we examined the longitudinal relationship between sugar and fat sensitivity, sugar and fat liking, habitual dietary intake, and BMI percentiles in a sample of 105 healthy-weight adolescents (baseline: BMI %tile 57.0 ± 24.3; age 14-16 years) over a 4-year period. Taste sensitivity was assessed via a triangle fat and sweet taste discrimination test. Taste liking were rated on a visual analog scale for four milkshakes that varied in sugar and fat contents (high-fat/high-sugar (HF/HS), low-fat/high-sugar (LF/HS), high-fat/low-sugar (HF/LS), low-fat/low-sugar (LF/LS) milkshakes). A modified version of the reduced Block Food Frequency Questionnaire (BFFQ) was used to assess dietary intake. All measurements were repeated annually. Repeated measures correlations and linear mixed effects models were used to model the associations between the variables. Sugar sensitivity was negatively associated with liking for the LF/HS milkshake over the 4-year period. Low sugar sensitivity at baseline predicted increases in BMI percentile over time, but this association didn't survive a correction for multiple comparisons. Percent daily intake from fat was positively associated with liking for the HF/HS milkshake and negatively associated with liking for the LF/LS milkshake over 4 years. Together, these results demonstrate that lower sensitivity to sweet taste is linked to increased hedonic response to high-sugar foods and increased energy intake from fat seems to condition adolescents to show increased liking for high-fat/high-sugar foods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Papantoni, Shearrer, Sadler, Stice and Burger.)

Objective: Obesity risk transmits from parents to children. Underlying neural mechanisms were investigated in this study by evaluating influences of familial obesity risk defined by maternal obesity and influences of current overweight on three indices of brain structure in adolescents., Methods: In total, 22 lean adolescents with lean mothers (lean low-risk), 25 lean adolescents with mothers with obesity/overweight (lean high-risk), and 36 adolescents with obesity/overweight underwent structural MRI scans for estimation of regional gray and white matter volume and cortical thickness., Results: The lean high-risk compared with the lean low-risk group demonstrated lower gray and white matter volume and cortical thickness in the postcentral gyrus (somatosensory cortex), lower gray and white matter volume in the opercular cortex (taste cortex), lower gray matter volume and cortical thickness in the anterior cingulate cortex, and lower cortical thickness in the precuneus. Comparisons of the lean and obesity/overweight groups revealed further structural alterations in the postcentral gyrus, posterior cingulate gyrus, and middle temporal gyrus., Conclusions: Familial obesity risk and current obesity/overweight were associated with overlapping and distinct patterns of brain structure alterations. Longitudinal studies are warranted to investigate whether structural changes associated with familial obesity risk predict future weight trajectories., (© 2020 The Obesity Society.)

BACKGROUNDBariatric surgeries are the most effective treatments for successful and sustained weight loss, but individuals vary in treatment response. Understanding the neurobiological and behavioral mechanisms accounting for this variation could lead to the development of personalized therapeutic approaches and improve treatment outcomes. The primary objectives of this study were to investigate changes in taste preferences and taste-induced brain responses after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) and to identify potential taste-related predictors of weight loss.METHODSFemales, ages 18 to 55, with a body mass index greater than or equal to 35 kg/m2, and approved for bariatric surgery at the Johns Hopkins Center for Bariatric Surgery were recruited for participation. Demographics, anthropometrics, liking ratings, and neural responses to varying concentrations of sucrose plus fat mixtures were assessed before and after surgery via visual analog scales and functional MRI.RESULTSBariatric surgery produced decreases in liking for sucrose-sweetened mixtures. Greater preference for sucrose-sweetened mixtures before surgery was associated with greater weight loss in RYGB, but not VSG. In the RYGB group only, individuals who showed lower taste-induced activation in the ventral tegmental area (VTA) before surgery and greater changes in taste-induced VTA activation 2 weeks following surgery experienced increased weight loss.CONCLUSIONThe anatomical and/or metabolic changes associated with RYGB may more effectively "reset" the neural processing of reward stimuli, thereby rescuing the blunted activation in the mesolimbic pathway found in patients with obesity. Further, these findings suggest that RYGB may be particularly effective in patients with a preference for sweet foods.FUNDINGNIH K23DK100559 and Dalio Philanthropies.

Body weight is substantially determined by eating behaviors, which are themselves driven by biological factors interacting with the environment. Previous studies in young children suggest that genetic influences on dopamine function may confer differential susceptibility to the environment in such a way that increases behavioral obesity risk in a lower socioeconomic status (SES) environment but decreases it in a higher SES environment. We aimed to test if this pattern of effect could also be observed in adolescence, another critical period for development in brain and behavior, using a novel measure of predicted expression of the dopamine receptor 4 (DRD4) gene in prefrontal cortex. In a sample of 76 adolescents (37 boys and 39 girls from Baltimore, Maryland/US, aged 14-18y), we estimated individual levels of DRD4 gene expression (PredDRD4) in prefrontal cortex from individual genomic data using PrediXcan, and tested interactions with a composite SES score derived from their annual household income, maternal education, food insecurity, perceived resource availability, and receipt of public assistance. Primary outcomes were snack intake during a multi-item ad libitum meal test, and food-related impulsivity assessed using a food-adapted go/no-go task. A linear regression model adjusted for sex, BMI z-score, and genetic ethnicity demonstrated a PredDRD4 by composite SES score interaction for snack intake (p = 0.009), such that adolescents who had lower PredDRD4 levels exhibited greater snack intake in the lower SES group, but lesser snack intake in the higher SES group. Exploratory analysis revealed a similar pattern for scores on the Perceived Stress Scale (p = 0.001) such that the low PredDRD4 group reported higher stress in the lower SES group, but less stress in the higher SES group, suggesting that PredDRD4 may act in part by affecting perceptions of the environment. These results are consistent with a differential susceptibility model in which genes influencing environmental responsiveness interact with environments varying in obesogenicity to confer behavioral obesity risk in a less favorable environment, but behavioral obesity protection in a favorable one., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the human brain and is implicated in several neuropathologies. Glutathione is a major antioxidant in the brain and is considered a marker of oxidative stress. Several studies have reported age-related declines in GABA levels in adulthood, but the trajectory of both GABA and glutathione during childhood has not been well explored. The aim of this study is to establish how GABA and glutathione vary with age during early development., Materials and Methods: Twenty-three healthy children (5.6-13.9 years of age) were recruited for this study. MR imaging/MR spectroscopy experiments were conducted on a 3T MR scanner. A 27-mL MR spectroscopy voxel was positioned in the frontal lobe. J-difference edited MR spectroscopy was used to spectrally edit GABA and glutathione. Data were analyzed using the Gannet software, and GABA+ (GABA + macromolecules/homocarnosine) and glutathione were quantified using water (GABA+ H2O and Glutathione H2O ) and Cr (GABA+/Cr and glutathione/Cr) as concentration references. Also, the relative gray matter contribution to the voxel volume (GM ratio ) was estimated from structural images. Pearson correlation coefficients were used to examine the association between age and GABA+ H2O (and glutathione H2O ), between age and GABA+/Cr (and glutathione/Cr), and between age and GM ratio ., Results: Both GABA+ H2O ( r  =   0.63, P  = .002) and GABA+/Cr ( r  =   0.48, P  = .026) significantly correlated with age, whereas glutathione measurements and GM ratio did not., Conclusions: We demonstrate increases in GABA and no differences in glutathione with age in a healthy pediatric sample. This study provides insight into neuronal maturation in children and may facilitate better understanding of normative behavioral development and the pathophysiology of developmental disorders., (© 2020 by American Journal of Neuroradiology.)