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Objective/methodsDNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals.ResultsWe identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two independent cohorts. Further, we identified six adipose tissue depot-specific genes (HAND2, HOXC6, PPARG, SORBS2, CD36, and CLDN1). The effects were further supported in additional independent cohorts. Our top hits might play a role in adipogenesis and differentiation, obesity, lipid metabolism, and adipose tissue expandability. Finally, we show that in vitro methylation of SORBS2 directly represses gene expression.ConclusionsTaken together, our data show distinct tissue specific epigenetic alterations which associate with obesity.

The objective of our study was to investigate the association between the initial levels of serum S-100B protein and neuron specific enolase and the severity of radiologically visible brain damage and outcome after severe head injury. Admission computed tomography (CT) scans of forty-four patients with severe head injury were analysed. Initial levels of S-100B protein and neuron specific enolase were compared between the different outcome groups at 6 month, the different categories of the Marshall classification, the presence of traumatic subarachnoid haemorrhage, the type of haematoma and the volume of contusion. Serum S-100B was significantly higher in patients with unfavourable outcome (1.1 micrograms/l versus 0.3 microgram/l, p < 0.005, Mann-Whitney U test). In diffuse injury, unfavourable outcome significantly increased with higher Marshall grades (p < 0.05). There was a significant correlation between the four grades of diffuse injury and initial serum S-100B protein (r = 0.48, p < 0.001). Patients with focal mass lesions and a favourable outcome after 6 month had significantly lower S-100B values than those who had an unfavourable outcome (0.51 microgram/l versus 1.3 micrograms/l, p < 0.05). A significant correlation was demonstrated between the volume of contusion visible on CT scans and serum S-100B (r = 0.58, p < 0.001). In our study, initial serum S-100B protein was a powerful predictor of outcome even within the same category of radiologically visible brain damage. Serum S-100B protein may provide independent information about the severity of primary brain damage after head injury.

BackgroundGenetic variants within the bitter taste receptor gene TAS2R38 are associated with sensitivity to bitter taste and are related to eating behavior in the Amish population. Sensitivity to bitter taste is further related to anthropometric traits in an genetically isolated Italian population. We tested whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939) may be related to eating behavior, anthropometric parameters, metabolic traits and consumer goods intake in the German Sorbs.Materials and MethodsThe three SNPs were genotyped in a total cohort of 1007 individuals (male/female: 405/602). The German version of the three-factor eating questionnaire was completed by 548 individuals. Genetic association analyses for smoking behavior, alcohol and coffee intake, eating behavior factors (restraint, disinhibition and hunger) and other metabolic traits were analyzed. Further, by combining the three SNPs we applied comparative haplotype analyses categorizing PAV (proline-alanine-valine) carriers (tasters) vs. homozygous AVI (alanin-valine-isoleucine) carriers (non-tasters).ResultsSignificant associations of genetic variants within TAS2R38 were identified with percentage of body fat, which were driven by associations in women. In men, we observed significant associations with 30 min plasma glucose, and area under the curve for plasma glucose (0–120 min) (all adjusted P≤0.05). Further, we found that carriers of at least one PAV allele show significantly lower cigarette smoking per day (P = 0.002) as well as, albeit non-significant, lower alcohol intake. We did not confirm previously reported associations between genetic variants of TAS2R38 and eating behavior.ConclusionOur data suggest that genetic variation in TAS2R38 is related to individual body composition measures and may further influence consumer goods intake in the Sorbs possibly via individual sensitivity to bitter taste.

Cerebellar liponeurocytoma is a newly recognized, rare clinicopathological entity. It manifests with posterior fossa symptoms in adults and is characterized histopathologically by advanced neuronal and focal lipomatous differentiation with a low level of mitotic activity. The authors analyzed the computerized tomography (CT) and magnetic resonance (MR) imaging findings in two patients with histopathologically proven cerebellar liponeurocytomas and review the literature. Cerebellar liponeurocytoma may be suspected on the basis of neuroimaging findings that demonstrate an intraaxial neoplasm with the propensity for exophytic growth into the adjacent subarachnoid spaces. On CT scans, the tumor commonly presents as a hypointense mass with intermingled areas exhibiting the attenuation values of fatty tissue. On T1-weighted MR images, the tumor is hypointense with scattered foci of hyperintense signal and displays moderate contrast enhancement. On T1-weighted MR images, the tumor is slightly hyperintense to cortex, and edema is usually absent. Areas of fat density as assessed on CT scans and of T1 hyperintensity seen on MR images help to distinguish this rare neoplasm from the more common adult medulloblastomas or ependymomas. The available follow-up data indicate a favorable clinical prognosis; therefore, knowledge and precise characterization of this tumor is important to avoid unnecessary adjuvant radio- or chemotherapy.

Background One of the major challenges in obesity treatment is to explain the high variability in the individual’s response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss. Methods We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m2) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity. Results Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change − 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10−5). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10− 4) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95–1.0] than predictors such as age and BMI (AUC ROC = 0.56). Conclusions Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.

Our data suggest that the variability in global methylation in adipose tissue might be related to alterations in glucose metabolism.

The beneficial effects of adiponectin and its negative correlation with BMI are well described. Adiponectin serum levels are altered in eating disorders such as anorexia nervosa, bulimia nervosa or binge eating. Here, we tested the hypothesis that (1) adiponectin serum levels correlate with human eating behavior factors and (2) that genetic variants of the ADIPOQ locus influence both serum levels and eating behavior. We analyzed 11 SNPs within ADIPOQ and in the 5 0 UTR and measured serum adiponectin levels in 1,036 individuals from the German Sorbs population. The German version of the three-factor eating questionnaire (FEV) was completed by 548 Sorbs. For replication purposes, we included an independent replication cohort from Germany (N = 350). In the Sorbs, we observed positive correlations of restraint with adiponectin serum levels (P = 0.001; r = 0.148) which, however, did not withstand adjustment for covariates (P = 0.083; r = 0.077). In addition, four SNPs were nominally associated with serum adiponectin levels (all P \ 0.05). Of these, two variants (rs3774261; rs1501229, all P \ 0.05) were also related to disinhibition. Furthermore, three variants were exclusively associated with hunger (rs2036373, P = 0.049) and disinhibition (rs822396; rs864265, all P \ 0.05). However, none of these associations withstood Bonferroni corrections for multiple testing (all P [ 9.3 9 10 -4 ). In our replication cohort, we observed similar effect directions at rs1501229 for disinhibition and hunger. A meta-analysis resulted in nominal statistical significance P = 0.036 (Z score 2.086) and P = 0.017 (Z score 2.366), respectively. Given the observed relationship of the SNPs with adiponectin levels and eating behavior, our data support a potential role of adiponectin in human eating behavior. Whether the relationship with eating behavior is mediated by the effects of circulating adiponectin warrants further investigations.