Age-Specific Quantification of Overweight/Obesity Risk Factors From Infancy to Adolescence and Differences by Educational Level of Parents.

Objectives: To explore the age-dependent associations between 26 risk factors and BMI in early life, and differences by parental educational level. Methods: Data of 10,310 children (24,155 measurements) aged 2-16 years participating in a multi-centre European cohort from 2007 to 2014 were utilized. Trajectories of overweight/obesity risk factors and their age-specific associations with BMI were estimated using polynomial mixed-effects models. Results: Exposure to most unfavourable factors was higher in the low/medium compared to the high education group, e.g., for PC/TV time (12.6 vs. 10.6 h/week). Trajectories of various risk factors markedly changed at an age of 9-11 years. Having a family history of obesity, maternal BMI, pregnancy weight gain and birth weight were positively associated with BMI trajectories throughout childhood/adolescence in both education groups; associations of behavioural factors with BMI were small. Parental unemployment and migrant background were positively associated with BMI in the low/medium education group. Conclusion: Associations of risk factors with BMI trajectories did not essentially differ by parental education except for social vulnerabilities. The age period of 9-11 years may be a sensitive period for adopting unfavourable behaviours.

Point-of-care applicable metabotyping using biofluid-specific electrospun MetaSAMPs directly amenable to ambient LA-REIMS.

In recent years, ambient ionization mass spectrometry (AIMS) including laser ablation rapid evaporation IMS, has enabled direct biofluid metabolome analysis. AIMS procedures are, however, still hampered by both analytical, i.e., matrix effects, and practical, i.e., sample transport stability, drawbacks that impede metabolome coverage. In this study, we aimed at developing biofluid-specific metabolome sampling membranes (MetaSAMPs) that offer a directly applicable and stabilizing substrate for AIMS. Customized rectal, salivary, and urinary MetaSAMPs consisting of electrospun (nano)fibrous membranes of blended hydrophilic (polyvinylpyrrolidone and polyacrylonitrile) and lipophilic (polystyrene) polymers supported metabolite absorption, adsorption, and desorption. Moreover, MetaSAMP demonstrated superior metabolome coverage and transport stability compared to crude biofluid analysis and was successfully validated in two pediatric cohorts (MetaBEAse, n = 234 and OPERA, n = 101). By integrating anthropometric and (patho)physiological with MetaSAMP-AIMS metabolome data, we obtained substantial weight-driven predictions and clinical correlations. In conclusion, MetaSAMP holds great clinical application potential for on-the-spot metabolic health stratification.

Stress Responsiveness and Emotional Eating Depend on Youngsters' Chronic Stress Level and Overweight.

The persistent coexistence of stress and paediatric obesity involves interrelated psychophysiological mechanisms, which are believed to function as a vicious circle. Here, a key mechanistic role is assumed for stress responsiveness and eating behaviour. After a stress induction by the Trier Social Stress Test in youngsters (n = 137, 50.4% boys, 6-18 years), specifically those high in chronic stress level and overweight (partial η2 = 0.03-0.07) exhibited increased stress vulnerability (stronger relative salivary cortisol reactivity and weaker happiness recovery) and higher fat/sweet snack intake, compared to the normal-weight and low-stress reference group. Stress responsiveness seems to stimulate unhealthy and emotional eating, i.e., strong cortisol reactivity was linked to higher fat/sweet snack intake (ß = 0.22) and weak autonomic system recovery was linked to high total and fat/sweet snack intake (ß = 0.2-0.3). Additionally, stress responsiveness acted as a moderator. As a result, stress responsiveness and emotional eating might be targets to prevent stress-induced overweight.

The Moderating Role of Emotion Regulation in the Association Between Stressors With Psychological and Biological Measures in Adolescence.

OBJECTIVE: This study explored the role of emotion regulation (ER) as a moderator in the stressor-adjustment outcome relationship while identifying the relevant stressors. METHODS: In 214 adolescents (10-18 years; 51.4% boys), stressors (parent and peer relations, negative events), psychological outcomes (adolescent perceived stress, psychopathology symptoms, negative affect), and biological measures related to the stress response (hair cortisol [HC], heart rate variability [HRV]) as well as ER strategies-maladaptive (MalER), adaptive (AdER), and their ratio (Mal/AdER)-were measured and analyzed via linear regression, adjusted for age, sex, and socioeconomic status. RESULTS: Parental rejection and bullying were the stressors with the strongest association with psychological outcomes (ß range = |0.217-0.352|, p < .05). In addition, parental rejection was associated with HC (ß = 0.242, p = .035), whereas none of the stressors were associated with HRV. MalER was linked to all, and AdER to most psychological outcomes (ß range = |0.21-0.49|, p < .05). MalER, but not AdER, was associated with HC (ß = 0.25, p = .009), whereas none of the ER strategy types were associated with HRV. Moreover, several associations between stressors and psychological outcomes were moderated by MalER and Mal/AdER, whereas AdER's role as a moderator was not confirmed. CONCLUSIONS: The study confirmed that adolescents' stressors are associated with both psychological and physiological outcomes and moderated by MalER or Mal/AdER. The lack of moderation by AdER directs toward the maladaptive shift theory. Investigations through a longitudinal, rather than a cross-sectional design, could further elucidate the current observations. Moreover, training in how to use ER effectively has a potential of increasing adolescents' stress resilience.

Rapid LA-REIMS and comprehensive UHPLC-HRMS for metabolic phenotyping of feces.

Ambient ionization-based techniques hold great potential for rapid point-of-care applicable metabolic fingerprinting of tissue and fluids. Hereby, feces represents a unique biospecimen as it integrates the complex interactions between the diet, gut microbiome and host, and is therefore ideally suited to study the involvement of the diet-gut microbiome axis in metabolic diseases and their treatments at a molecular level. We present a new method for rapid (<10 s) metabolic fingerprinting of feces, i.e. laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) with an Nd:YAG laser (2940 nm) and quadrupole Time-of-Flight mass spectrometer as main components. The LA-REIMS method was implemented on mimicked crude feces samples from individuals that were assigned a state of type 2 diabetes or euglycaemia. Based on the generated fingerprints, enclosing 4923 feature ions, significant segregation according to disease classification was achieved through orthogonal partial least squares discriminant analysis (Q2(Y) of 0.734 and p-value of 1.93e-17) and endorsed by a general classification accuracy of 90.5%. A comparison between the discriminative performance of the novel LA-REIMS and our established ultra-high performance liquid-chromatography high-resolution MS (UHPLC-HRMS) metabolomics and lipidomics methodologies for fingerprinting of stool was performed. Based on the supervised modelling results upon UHPLC-HRMS (Q2(Y) ≥ 0.655 and p-value ≤ 4.11 e-5), equivalent or better discriminative performance of LA-REIMS fingerprinting was concluded. Eventually, comprehensive UHPLC-HRMS was employed to assess metabolic alterations as observed for the defined classes, whereby metformin treatment of the type 2 diabetes patients was considered a relevant study factor to acquire new mechanistic insights. More specifically, ten metabolization products of metformin were identified, with (hydroxylated) triazepinone and metformin-cholesterol reported for the first time in vivo.In conclusion, LA-REIMS was established as an expedient strategy for rapid metabolic fingerprinting of feces, whereby potential implementations may relate, but are not limited to differential diagnosis and treatment efficacy evaluation of metabolic diseases. Yet, LC-HRMS remains essential for in-depth biological interpretation.

Validated Ultra-High-Performance Liquid Chromatography Hybrid High-Resolution Mass Spectrometry and Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry for Salivary Metabolomics.

Whereas urine and blood are typically targeted in clinical research, saliva represents an interesting alternative because its intrinsic metabolome is chemically diverse and reflective for various biological processes. Moreover, saliva collection is easy and noninvasive, which is especially valuable for cohorts in which sample collection is challenging, for example, infants and children. With this rationale, we established a validated ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) method for salivary metabolic profiling and fingerprinting. Hereby, 450 µL of saliva was centrifuged and passed over a 0.45-µm polyamide membrane filter, after which the extract was subjected to chromatographic analysis (HSS T3 column) and Q-Exactive Orbitrap-MS. For the majority of the profiled metabolites, good linearity (R2 ≥ 0.99) and precision (coefficient of variance ≤ 15%) was achieved. The fingerprinting performance was evaluated based on the complete metabolome (11 385 components), whereby 76.8% was found compliant with the criteria for precision (coefficient of variance ≤ 30%) and 82.7% with linearity (R2 ≥ 0.99). In addition, the method was proven fit-for-purpose for a cohort of 140 adolescents (6-16 years, stratified according to weight), yielding relevant profiles (45 obesity-related metabolites) and discriminative fingerprints (Q2 of 0.784 for supervised discriminant analysis). Alternatively, laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) was established for rapid fingerprinting of saliva, thereby using a Nd:YAG laser and Xevo G2-XS QToF-MS. With an acquisition time of 0.5 min per sample, LA-REIMS offers unique opportunities for point-of-care applications. In conclusion, this work presents a platform of UHPLC-HRMS and LA-REIMS, complementing each other to perform salivary metabolomics.

Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor.

The phytoestrogen resveratrol has been reported to possess cancer chemo-preventive activity on the basis of its effects on tumor cell lines and xenograft or carcinogen-inducible in vivo models. Here we investigated the effects of resveratrol on spontaneous mammary carcinogenesis using Δ16HER2 mice as HER2+/ERα+ breast cancer model. Instead of inhibiting tumor growth, resveratrol treatment (0.0001% in drinking water; daily intake of 4µg/mouse) shortened tumor latency and enhanced tumor multiplicity in Δ16HER2 mice. This in vivo tumor-promoting effect of resveratrol was associated with up-regulation of Δ16HER2 and down-regulation of ERα protein levels and was recapitulated in vitro by murine (CAM6) and human (BT474) tumor cell lines. Our results demonstrate that resveratrol, acting as a proteasome inhibitor, leads to Δ16HER2 accumulation which favors the formation of Δ16HER2/HER3 heterodimers. The consequential activation of downstream mTORC1/p70S6K/4EBP1 pathway triggers cancer growth and proliferation. This study provides evidence that resveratrol mechanism of action (and hence its effects) depends on the intrinsic molecular properties of the cancer model under investigation, exerting a tumor-promoting effect in luminal B breast cancer subtype models.