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• Prenatal PFAS exposure was associated with elevated risk of obesity in 10-year-old children. • The obesogenic effects related to PFAS were more pronounced in girls. • PFAS exposure was linked to perturbation in several metabolic pathways. • Dysregulation of amino acid-related pathways may contribute to PFAS-induced obesity. Per- and polyfluoroalkyl substances (PFAS) have been suspected as potential environmental obesogens, with several mechanisms being proposed, including the role of metabolomics. However, current epidemiological studies have yielded inconclusive findings. We aimed to estimate the associations of prenatal exposure to PFAS with offspring adiposity measures, and to explore the potential metabolic pathways underlying these associations. A total of 464 mother–child pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. Cord serum concentrations of 12 PFAS and urine metabolite profiles at age 10 were obtained from the SMBCS database. Adiposity-related anthropometric measurements and body composition estimates of children aged 10 were used to assess offspring obesity. Multiple linear regression models and quantile g-computation were conducted to estimate the associations of prenatal exposure to individual and multiple PFAS with obesity at 10 years old. Metabolomics analysis was performed to characterize the biological pathways associated with PFAS exposure or obesity, subsequently identifying the overlapping metabolic pathways underlying the PFAS-obesity relationship. Prenatal exposure to several PFAS was significantly associated with elevated obesity-related markers in 10-year-old children. After stratification by sex, the effects were more pronounced in girls. Quantile g-computation results indicated that exposure to higher levels of PFAS mixtures during pregnancy was associated with increased odds of obesity in girls, with PFNA emerging as the predominant driving compound. Untargeted metabolomics results showed that several amino acid metabolic pathways were characterized as the overlapping pathways underlying the above associations. Taken together, our findings suggested the potential obesogenic effects of prenatal exposure to PFAS and offered insight into the possible metabolic mechanisms underlying PFAS-related offspring obesity. [ABSTRACT FROM AUTHOR]

Obesity in children contributes to higher risks of various chronic diseases in adulthood and the prevalence has increased worldwide including Japan. This study aims to examine the association between sleep duration at night in children aged 2.5 years and the subsequent risk of obesity at age 5.5 years. This study is embedded in the Longitudinal Survey on Babies Born in the 21st Century, which recruited families who had a child born in Japan in 2001. The multivariable logistic regression models were applied to calculate odds ratios (OR) and 95 % confidence intervals (CI) of childhood obesity at 5.5 years, defined as percentage of overweight (POW) ≥ 20 % and body mass index (BMI) ≥ 95th percentile of this study population according to sleep duration at night collected at 2.5 years child age. Among 25,378 children, 2.6 % and 3.7 % were obese at age 5.5 years defined by POW and BMI respectively. Compared with night sleep duration > 11 h/d, shorter sleep durations in 2.5 years-old children were associated with higher risk of obesity at 5.5 years; the multivariable ORs (95 %CI) were 1.05 (0.81–1.35), 1.23 (0.93–1.62) and 1.54 (1.04–2.31) for sleep duration 10, 9 and ≤ 8 h/d, respectively; p -trend = 0.03. The observed association differed according to the children (child's sex, napping habits, and children frequently play at park), and family characteristics (mother's age at delivery and mother's level of education). Short night sleep duration among girls aged 2.5 years was associated with risk of obesity at age 5.5 years, suggesting the importance of sufficient sleep duration at night for the prevention of obesity. • Short night sleep aged 2.5 years was associated with risk of obesity at age 5.5 years. • Girls with poor night's sleep duration appear to be at greater risk of obesity • Children with regular napping, who rarely or never played at a park, and whose mothers had younger ages at delivery and less education appear to be more at risk for obesity. [ABSTRACT FROM AUTHOR]

Perilipin 2 (PLIN2) regulates intracellular lipid metabolism in macrophages, and thus, plays a role in atherosclerosis. Aim of the study was to evaluate whether PLIN2 dysregulation is involved in the onset of preclinical atherosclerosis in children with overweight/obesity and to explore dysregulation mechanisms. Sixty-three children with overweight/obesity and 21 normal weight children (controls) of the same age and sex were enrolled. Carotid intima media thickness (cIMT) was evaluated; mRNA expression of PLIN2 and proteasome subunits (PSMD3 , PSMC4) was determined by Real Time PCR, and protein expression of PLIN2, LAMP2A and Hsc70 by Western blot analysis; fluorimetric assay was used to measure proteasome chymotrypsin like activity. We performed transient LAMP2A downregulation by siRNA and quantified intracellular lipids in monocytes by Nile Red staining and flow cytometry analysis. PLIN2 protein levels were significantly higher in children with overweight/obesity and correlated with cIMT after adjusting for confounders. Accordingly, monocytes of children with overweight/obesity showed a higher intracellular amount of lipids compared with controls. mRNA expression of the regulatory subunits PSMC4 and PSMD3 and proteasome activity were lower in children with overweight/obesity, while expression of LAMP2A and Hsc70 proteins, which belong to the chaperone-mediated autophagy (CMA) pathway, was not different, suggesting that PLIN2 dysregulation in monocytes was due to an impairment of proteasome efficiency and was not CMA related. PLIN2 was overexpressed in monocytes of children with overweight/obesity and could contribute to the onset of arteropathy. Our data suggest that proteasome impairment could contribute to PLIN2 overexpression. [Display omitted] • Lipid droplets Plin2 protein is overexpressed in monocytes of children with obesity. • Early arterial injury in children with obesity is associated with increased Plin2 protein expression in monocytes. • Plin2 upregulation could depend on proteasome impairment in children with obesity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Heart rate variability in eutrophic, overweight and obese children. • Remote monitoring of heart rate with smartphone. • Internet-of-things applied to health awareness. Heart rate variability (HRV) is a measurement of time variation between heartbeats. HRV analysis in children and adolescents with overweight and obesity is used as an indicator of cardiovascular system function. Because of that it is important to monitor HR with a non-invasive and reliable method. This paper describes a less traumatic and non-expensive method for online monitoring of HR and calculation of HRV parameters in eutrophic, overweight and obese children. Cardiac activity from eutrophic (n = 6), overweight (n = 11), and obese (n = 9) children, (10.3 ± 1.3 years old) were performed with a smartphone App connected via Bluetooth to a smartwatch sensor during night-, morning- and afternoon/evening-time for sixty days. Signals were transmitted from the smartphone to an online monitoring system. HRV analysis was performed on the web platform, eighteen parameters were calculated (time domain, frequency domain, Poincaré Plot and Sample Entropy). Normality, Two-way repeated measures Anova and Bonferroni tests were applied, p < 0.05 were considered statistically significant. Each group showed statistical differences in the time domain parameters SDNN and RMSDD, p < 0.05 in all cases. The parameters SD2 and ratio SD1-SD2 were significantly different in all cases (p < 0.05). Likewise, there were differences between night-, morning- and afternoon/evening-time for all groups in the same parameters SDNN and RMSDD (p < 0.05 in all cases) and SD2 (p < 0.05), while the ratio SD1-SD2 was marginally significant (p = 0.052). The described methodology provides a new, inexpensive and easy to implement approach for remote monitoring and analysis of cardiovascular parameters from children. [ABSTRACT FROM AUTHOR]