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This study of the dynamics of BMI in children from birth to adolescence assessed the age of susceptibility for sustained obesity and of onset of obesity. The most rapid weight gain occurred between 2 and 6 years of age; obesity at that age forecast obesity in adolescence.

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FLII) and leucine-rich-repeat-(in FLII)-interacting-protein-1 as a regulatory complex for UCP1 transcription. Physiologically, FGF6/9 expression in adipose is upregulated by exercise and cold in mice, and FGF9/FGFR3 expression in human neck fat is significantly associated with UCP1 expression. Loss of FGF9 impairs BAT thermogenesis. In vivo administration of FGF9 increases UCP1 expression and thermogenic capacity. Thus, FGF6 and FGF9 are adipokines that can regulate UCP1 through a transcriptional network that is dissociated from brown adipogenesis, and act to modulate systemic energy metabolism. Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.

Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children.

Background/ObjectivesThere is a concern that measures aiming to limit a further spread of COVID-19, e.g., school closures and social distancing, cause an aggravation of the childhood obesity epidemic. Therefore, we compared BMI trends during the 15 years before and during the COVID-19 pandemic.Subjects/MethodsTo assess the change in weight dynamics during the first months of COVID-19, we compared the trends of 3-month change in BMI-SDS (ΔBMI-SDS) and the proportions of children showing a high positive (HPC) or high negative (HNC) weight change between 2005 and 2019 and the respective changes from 2019 (pre-pandemic) to 2020 (after the onset of anti-pandemic measures) in more than 150,000 children (9689 during the pandemic period). The period of 3 months corresponds approximately to the first lockdown period in Germany.ResultsDuring the COVID-19 pandemic, we found a substantial weight gain across all weight and age groups, reflected by an increase in the 3-month change in BMI-SDS (β = 0.05, p < 0.001), an increase in the proportion of children showing HPC (OR = 1.4, p < 0.001), and a decrease in the proportion of children showing HNC (OR = 0.7, p < 0.001). Besides, we found the same trends since 2005 on a low but stable level with a yearly increase of ΔBMI-SDS by β = 0.001 (p < 0.001), the odds of HPC increased by ORhigh_pos = 1.01 (p < 0.001), and the odds of HNC decreased by ORhigh_neg = 0.99 (p < 0.001). These rather small effects accumulated to β = 0.02, ORhigh_pos = 1.14, and ORhigh_pos = 0.85 over the whole period 2005–2019. Alarmingly, both the long-term and the short-term effects were most pronounced in the obese subgroup.ConclusionsThere are positive dynamics in different measures of weight change, indicating a positive trend in weight gain patterns, especially within the group of children with obesity. These dynamics are likely to be escalated by COVID-19-related measures. Thus, they may lead to a significant further aggravation of the childhood obesity pandemic.

The familial social background of a child can significantly impact their behavior and health. We investigated associations between socio-economic status (SES) and health parameters and behaviors in German children and adolescents. Data were collected between 2011 and 2018 in the framework of the LIFE Child study. Participants included 2998 children aged 3–18 years. SES was represented by an index combining information on parental education, occupation, and income. Associations between SES and health outcomes were estimated using linear and logistic regression analyses. In a moderator analysis, all associations were checked for interactions between SES and age or sex. A higher SES composite score was associated with better health (lower body mass index (β = −0.26), fewer behavioral difficulties (β = −0.18), higher quality of life (β = 0.21), fewer critical life events (odds ratio (OR) = 0.93); all p < 0.05) and a healthier lifestyle (healthier nutrition (β = 0.16), less excessive television use (OR = 0.87), less nicotine consumption (OR = 0.93), and more physical activity (OR = 1.18); all p < 0.05). However, SES was not associated with alcohol consumption (OR = 1.02) or sleep problems (β = −0.04). The strengths of the associations between SES and child health did not differ depending on SES indicator (education, occupation, income). The associations between SES and parent-reported behavioral difficulties and physical activity were stronger in older vs. younger children. In contrast, none of the observed associations were moderated by sex. This study highlights the strong association between socio-economic status and child health, even in modern Western societies.

Background Exposure to endocrine-disrupting chemicals can alter normal physiology and increase susceptibility to non-communicable diseases like obesity. Especially the prenatal and early postnatal period is highly vulnerable to adverse effects by environmental exposure, promoting developmental reprogramming by epigenetic alterations. To obtain a deeper insight into the role of prenatal bisphenol A (BPA) exposure in children’s overweight development, we combine epidemiological data with experimental models and BPA-dependent DNA methylation changes. Methods BPA concentrations were measured in maternal urine samples of the LINA mother-child-study obtained during pregnancy ( n  = 552), and BPA-associated changes in cord blood DNA methylation were analyzed by Illumina Infinium HumanMethylation450 BeadChip arrays ( n  = 472). Methylation changes were verified by targeted MassARRAY analyses, assessed for their functional translation by qPCR and correlated with children’s body mass index (BMI) z scores at the age of 1 and 6 years. Further, female BALB/c mice were exposed to BPA from 1 week before mating until delivery, and weight development of their pups was monitored ( n  ≥ 8/group). Additionally, human adipose-derived mesenchymal stem cells were treated with BPA during the adipocyte differentiation period and assessed for exposure-related epigenetic, transcriptional and morphological changes ( n  = 4). Results In prenatally BPA-exposed children two CpG sites with deviating cord blood DNA-methylation profiles were identified, among them a hypo-methylated CpG in the promoter of the obesity-associated mesoderm-specific transcript ( MEST) . A mediator analysis suggested that prenatal BPA exposure was connected to cord blood MEST promoter methylation and MEST expression as well as BMI z scores in early infancy. This effect could be confirmed in mice in which prenatal BPA exposure altered Mest promoter methylation and transcription with a concomitant increase in the body weight of the juvenile offspring. An experimental model of in vitro differentiated human mesenchymal stem cells also revealed an epigenetically induced MEST expression and enhanced adipogenesis following BPA exposure. Conclusions Our study provides evidence that MEST mediates the impact of prenatal BPA exposure on long-term body weight development in offspring by triggering adipocyte differentiation.

In spring 2020, the first Covid-19-related lockdown included the closing of kindergartens and schools. Home schooling, the lack of social contacts with peers and the care of the children at home posed an enormous challenge for many families. The present study investigated the leisure behavior of 285 one- to 10-year-old German children at two time points (t1 and t2) during the Covid-19-related lockdown in spring 2020. In the subsample of primary school children (n = 102), we also explored children's attitudes towards schoolwork at home. Analyses focused on the change of behavior from t1 to t2, on differences in these changes depending on socio-economic status (SES), and on associations of behavior with SES, the number of children at home, and the frequency of receiving learning materials from school. While the frequency of playing outside increased significantly from t1 to t2, the frequency of handicrafts, playing board games, indoor sports, and motivation to do schoolwork decreased. The observed changes between t1 and t2 did not differ depending on SES. However, a lower SES was associated with higher media use, less outdoor activity, and (though only marginally significant) a reduced time doing schoolwork and a reduced ability to concentrate on schoolwork at t1. In households with more children, children played outside more often, but were read to less frequently and (though only marginally significant) watched movies and series less frequently. Children receiving learning materials from school on a regular basis spent significantly more time doing schoolwork at home than children receiving materials only irregularly. A continuing loss of childcare in day-care facilities and schools entails the danger of declining education in the form of (inter)active indoor activities and schoolwork.

Background Blood-based DNA methylation has been linked to obesity and metabolic health, yet its relationship to adipose tissue function remains incompletely understood. This study aimed to investigate the epigenetic regulation of EIF5A (Eukaryotic translation initiation factor 5A-1 ) and TGIF1 (TGFB Induced Factor Homeobox 1) across blood and adipose tissue in obesity. Methods Candidate genes were identified using a multi-step gene selection approach integrating transcriptomic and epigenomic data from blood and adipose tissue samples obtained from children and adults across four diverse population- and disease-focused cohorts. Genes were prioritized based on differential DNA methylation and gene expression in obesity. Targeted bisulfite sequencing of EIF5A and TGIF1 was conducted in blood samples from adults across BMI-defined groups and from children prior to the development of obesity, to validate candidate loci and to examine associations with metabolic and adipocyte-related phenotypes. Results In adults from the Leipzig Obesity BioBank, blood DNA methylation ( N  = 150) of both EIF5A and TGIF1 was significantly increased in individuals with obesity. EIF5A mRNA expression ( N  = 1554) was significantly higher in omental-visceral adipose tissue compared with subcutaneous adipose tissue. Blood DNA methylation of EIF5A was associated with body mass index (BMI), glycated hemoglobin (HbA1c), and leukocyte counts, particularly among individuals with type 2 diabetes mellitus. In children, blood DNA methylation ( N  = 75) of EIF5A was associated with longitudinal HbA1c trajectories. For TGIF1 , DNA methylation levels were increased in subcutaneous adipose tissue ( N  = 219) of children with obesity and correlated with fasting serum insulin concentrations. Across cohorts, TGIF1 regulation in both blood and adipose tissue showed consistent associations with adipocyte size. Notably, blood DNA methylation of TGIF1 in childhood was associated with body fat mass and HbA1c at later follow-up despite normal weight at baseline. Conclusion EIF5A and TGIF1 DNA methylation represent cross-tissue epigenetic signatures linking blood-based DNA methylation to adipose tissue dysfunction, adipocyte hypertrophy, and early metabolic risk. These findings support the potential of blood DNA methylation markers to reflect adipose tissue health and metabolic outcomes across the lifespan.

Background Even though the transition from adolescence to adulthood is a vulnerable and crucial period for young individuals with chronic conditions, it remains poorly studied in obesity. We comprehensively characterized the transition of children with overweight/obesity from childhood to adult care. Methods Data from an adulthood follow-up of the Leipzig childhood obesity cohort ( N  = 209, mean age at follow-up 24.9 years) were analyzed and related to the respective childhood data. Assessments comprised anthropometrics, oral glucose tolerance testing, carotid ultrasonography, 24 h blood pressure monitoring, liver elastography and questionnaires on psychosocial background, quality of life and transition process. Results Here we show that childhood onset overweight/obesity persists in 93.3% until adulthood. However, most patients (55.6%) who move into a higher BMI category during transition still report that things are going better with their weight during adulthood. Complications are frequent among young adults (overall 83.7%, (pre)diabetes 11.4%, hypertension 24.5%, elevated intima-media thickness 82.2%, fatty liver disease 10.2%, regular intake of medication 45%) and deteriorate with progressing weight gain from childhood to adulthood. 87% of adults have not been aware of one or more of these complications before. Most participants report physical complaints (57.3%) and symptoms of depression/anxiety (52.0%). The majority (94.3%) lose contact with specialized obesity care during transition with lack of knowledge being the most frequent reason. Instead, general practitioners are regularly consulted by 50.7%, but obesity is seldom addressed as a topic (22.6%). Better management of the transition process is desired by 26.7% of participants. Conclusions Children with overweight/obesity carry a substantial health burden into adulthood which is often not perceived. Structured transition approaches are needed to address obesity as a chronic condition. Plain language summary Young people with obesity often continue to have weight issues into adulthood, however they have been poorly followed so far. In our study, we conducted a follow-up of children with obesity at young adulthood. We revealed that health complications such as diabetes, high blood pressure, and fatty liver disease are common, yet many remain unaware. Many also experience physical discomfort and mental health struggles. Most lose contact with obesity specialists, relying instead on general doctors, who rarely discuss obesity. A quarter of participants wanted better support during the transition to adulthood. The study highlights the need for structured programs to help manage obesity as a long-term condition. Riedel et al. follow up children with obesity when they become young adults. Although obesity persists in most cases with serious complications already present, most participants do not accurately perceive their health burden and have lost contact with the healthcare system.