Project description:Here we studied the epigenetic regulation of the naïve CD4+ T-cell activation response among children with IgE-mediated food allergy. Using integrated DNA methylation and transcriptomic profiling, we found that food allergy in infancy is associated with dysregulation of T-cell activation genes. Reduced expression of cell cycle related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) were associated with poorer T-lymphoproliferative responses in infancy after polyclonal activation of the T-cell receptor.
Project description:Effects of current therapeutic foods in undernourished Bangladeshi children compared to microbiota-directed food prototypes in gnotobiotic mice and piglets
Project description:Here we studied the epigenetic regulation of the naïve CD4+ T-cell activation response among children with IgE-mediated food allergy. Using integrated DNA methylation and transcriptomic profiling, we found that food allergy in infancy is associated with dysregulation of T-cell activation genes. Reduced expression of cell cycle related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) were associated with poorer T-lymphoproliferative responses in infancy after polyclonal activation of the T-cell receptor.
Project description:BackgroundWhile neuroimaging studies have revealed that reward dysfunction may similarly contribute to obesity and addiction, no prior studies have examined neural responses in individuals who meet the "clinical" food addiction phenotype.MethodsWomen (n = 44) with overweight and obesity, nearly half of whom (n = 20) met criteria for moderate-to-severe Yale Food Addiction Scale 2.0 (YFAS 2.0) food addiction, participated in a functional magnetic resonance imaging cue reactivity task. Participants viewed images of highly processed foods, minimally processed foods, and household objects while thinking about how much they wanted each item. Differences in neural responses by YFAS 2.0 food addiction to highly processed and minimally processed food cues were investigated.ResultsThere was a significant interaction between participant group and neural response in the right superior frontal gyrus to highly versus minimally processed food cues (r = 0.57). Individuals with YFAS 2.0 food addiction exhibited modest, elevated responses in the superior frontal gyrus for highly processed food images and more robust, decreased activations for minimally processed food cues, whereas participants in the control group showed the opposite responses in this region. Across all participants, the household items elicited greater activation than the food cues in regions associated with interoceptive awareness and visuospatial attention (e.g., insula, inferior frontal gyrus, inferior parietal lobe).ConclusionsWomen with overweight or obesity and YFAS 2.0 food addiction, compared to those with only overweight or obesity, exhibited differential responses to highly and minimally processed food cues in a region previously associated with cue-induced craving in persons with a substance-use disorder. Overall, the present work provides further support for the utility of the food addiction phenotype within overweight and obesity.
Project description:Genome wide DNA methylation profiling study of PBMC from 71 unique primary patient blood samples. The Illumina Human Methylation 450k array was used. 29 challenge proven food allergy, 29 sensitized but oral tolerant, 13 non food allergics Mixture of food allergy phenotypes (egg allergic (15), peanut allergic (14)), food sensitization phenotypes (egg sensitized (14), peanut sensitized (15)). 4 samples had technical replicate hybridzations. Bisulphite converted DNA from the 75 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2. Technical replicates were combined during processing, resulting in normalized Beta values for 71 unique primary patient blood samples.
Project description:There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity-an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.
Project description:Obesity and smoking constitute two of the main causes of preventable deaths in the developed countries today. Many smokers motivate consumption as a means to control their body weight because smoking cessation increases the risk to gain weight. Although it is well established that nicotine reduces feeding in animals and that smoking is associated with reduced body weight in quasi-experimental studies of humans, acute nicotine effects are mixed and little is known about the brain networks supporting these effects. Thus, we investigated 26 normal-weighted never-smokers who received either nicotine (2?mg) or placebo gums following a double-blinded randomized cross-over design. We used functional magnetic resonance imaging (fMRI) to investigate reactivity to palatable food cues after both overnight fasting and following a standardized caloric intake (75?g oral glucose tolerance test (OGTT)). Participants viewed food or low-level control pictures in a block design and rated their current appetite after each block. Nicotine had a small- to medium-sized effect on subjective appetite and significantly altered food-cue reactivity in a region sensitive to caloric intake that extended from the right hypothalamus to the basal ganglia. During placebo sessions, the OGTT reduced functional coupling of this region with a 'salience network' (ie, amygdala, ventromedial prefrontal cortex) in processing of food pictures. Furthermore, nicotine reduced coupling with the nucleus accumbens and the OGTT reduced coupling with an 'interoceptive network' (ie, insula, operculum) instead. We conclude that locally restricted acute effects of nicotine in the hypothalamic area have profound effects on food-processing networks.