Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults.

BACKGROUND: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. METHODS: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5-19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). FINDINGS: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. INTERPRETATION: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. FUNDING: UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union.

Once-Weekly Semaglutide in Adolescents with Obesity.

BACKGROUND: A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking. METHODS: In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68. RESULTS: A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was -16.1% with semaglutide and 0.6% with placebo (estimated difference, -16.7 percentage points; 95% confidence interval [CI], -20.3 to -13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group. CONCLUSIONS: Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.).

Obesity-induced thymic involution and cancer risk.

Declining thymic functions associated either with old age (i.e., age-related thymic involution), or with acute involution as a result of stress, infectious disease, or cytoreductive therapies (e.g., chemotherapy/radiotherapy), have been associated with cancer development. A key mechanism underlying such increased cancer risk is the thymus-dependent debilitation of adaptive immunity, which is responsible for orchestrating immunoediting mechanisms and tumor immune surveillance. In the past few years, a blooming set of evidence has intriguingly linked obesity with cancer development and progression. The majority of such studies has focused on obesity-driven chronic inflammation, steroid/sex hormone and adipokine production, and hyperinsulinemia, as principal factors affecting the tumor microenvironment and driving the development of primary malignancy. However, experimental observations about the negative impact of obesity on T cell development and maturation have existed for more than half a century. Here, we critically discuss the molecular and cellular mechanisms of obesity-driven thymic involution as a previously underrepresented intermediary pathology leading to cancer development and progression. This knowledge could be especially relevant in the context of childhood obesity, because impaired thymic function in young individuals leads to immune system abnormalities, and predisposes to various pediatric cancers. A thorough understanding behind the molecular and cellular circuitries governing obesity-induced thymic involution could therefore help towards the rationalized development of targeted thymic regeneration strategies for obese individuals at high risk of cancer development.

Child-to-adult body size change and risk of type 2 diabetes and cardiovascular disease.

AIMS/HYPOTHESIS: Childhood overweight increases the risk of type 2 diabetes and cardiovascular disease in adulthood. However, the impact of childhood leanness on adult obesity and disease risk has been overlooked. We examined the independent and combined influences of child and adult body size on the risk of type 2 diabetes and cardiovascular disease. METHODS: Data from the UK Biobank on 364,695 individuals of European ancestry and free of type 2 diabetes and cardiovascular disease were divided into nine categories based on their self-reported body size at age 10 and measured BMI in adulthood. After a median follow-up of 12.8 years, 33,460 individuals had developed type 2 diabetes and/or cardiovascular disease. We used Cox regression models to assess the associations of body size categories with disease incidence. RESULTS: Individuals with low body size in childhood and high body size in adulthood had the highest risk of type 2 diabetes (HR 4.73; 95% CI 4.50, 4.99), compared to those with average body size in both childhood and adulthood. This was significantly higher than the risk in those with high body size in both childhood and adulthood (HR 4.05; 95% CI 3.84, 4.26). By contrast, cardiovascular disease risk was determined by adult body size, irrespective of childhood body size. CONCLUSIONS/INTERPRETATION: Low body size in childhood exacerbates the risk of type 2 diabetes associated with adult obesity but not the risk of cardiovascular disease. Thus, promoting healthy weight management from childhood to adulthood, among lean children, is crucial.

Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

BACKGROUND: Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. METHODS AND FINDINGS: We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. CONCLUSIONS: Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. WHY WAS THIS STUDY DONE?: - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. WHAT DID THE RESEARCHERS DO AND FIND?: - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. WHAT DO THESE FINDINGS MEAN?: - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Single-dose azithromycin for infant growth in Burkina Faso: Prespecified secondary anthropometric outcomes from a randomized controlled trial.

BACKGROUND: Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso. METHODS AND FINDINGS: Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) -0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI -0.05 to 0.06), WAZ (mean difference -0.004 SD, 95% CI -0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI -0.03 to 0.03), LAZ (mean difference -0.005 SD, 95% CI -0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI -0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth. CONCLUSIONS: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03676764.

Reflecting on parental insights into healthy lifestyles: a qualitative study.

BACKGROUND: Children living in the most deprived regions are more than twice as likely as their affluent peers to be obese. One way we can explain the social gradient of health (determined by relative position on the scale of social disadvantage or advantage) is by identifying the barriers and drivers to health that different groups of people experience. This study explored the understanding and perceptions of (and barriers and drivers to) a healthy lifestyle to investigate how commissioned services can better support residents to enable behaviour change in an area of high social deprivation. This community engagement activity was also conducted to inform commissioning decisions in children's public health services. METHODS: We used a qualitative study design with a semi-structured interview schedule. Four focus groups (5-8 participants, n=26) were conducted in an area of high deprivation in northwest England. Parents or carers were invited to attend anonymously by the Public Health Community Engagement Officer (in June 2022). The inclusion criteria were previous attendance on a weight management programme. Data were analysed using thematic analysis. Engagement activities do not require ethics approval. All participants provided written informed consent to take part. No further information was collected about personal characteristics. FINDINGS: The study participants demonstrated an awareness and understanding of factors affecting child and family health and health behaviours: healthy eating, exercise, mental health and emotional wellbeing, family values and attitudes towards a healthy lifestyle, cooking and budgeting, wider social connections, access to open spaces, availability of local activities, costs (including hidden costs), and structural barriers. INTERPRETATION: Using the finding that participants recognise barriers and drivers to behaviour change beyond knowledge and skills, we reflect on why there was no take up for a commissioned intervention that aimed to address childhood obesity in the Lancashire area. These reflections inform arguments for an alternative model of service commission that relies less on established randomised trial evidence base and more on participatory codesign and a place-based approach (working with populations' existing knowledge and skills) and is particularly sensitive to people's own perception of the specific drivers and barriers they experience to behaviour change. Limitations include sampling from an area with low diversity and selection of participants who have previously agreed to uptake a weight management intervention. FUNDING: None.

Obesity-Associated GNAS Mutations and the Melanocortin Pathway.

BACKGROUND: GNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism). METHODS: We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. RESULTS: Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P = 0.004). CONCLUSIONS: Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).

Postnatal feeding with high-fat combined with high-glucose diet induces precocious puberty in Sprague‒Dawley rat pups.

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

More than a Nuisance: Implications of Food Marketing for Public Health Efforts to Curb Childhood Obesity.

Fifteen years ago, public health experts urged industry, governments, and advocates to take action to dramatically improve the unhealthy food-marketing environment surrounding children in order to address the global childhood obesity crisis. Since then, research has confirmed that food marketing to children has far-reaching negative effects on their diets and health, takes advantage of adolescent vulnerabilities, and contributes to health disparities. In addition, digital marketing has profoundly changed young people's engagement with brands. Moreover, reliance on industry self-regulation as a solution has proven ineffective. Government-led policies have been more successful, but they remain limited in scope and challenging to adopt and implement. New approaches are necessary to increase public and policy maker awareness that food marketing is more than a nuisance, that it threatens the long-term health of children and adolescents worldwide, and that meaningful governmental action is urgently required to curtail industry's negative impact on young people's well-being.

The effectiveness of group-based, parent-only weight management interventions for children and the factors associated with outcomes: a systematic review.

BACKGROUND: Obesity in Childhood is a significant public health issue, which requires both a preventative and treatment approach. International guidelines continue to recommend family-focused, multicomponent, childhood weight management programmes and many studies have investigated their effectiveness, however, findings have been mixed and primarily based on weight. Thus, the aim of this review was to assess the effectiveness of group-based parent-only interventions on a broad range of child health-related outcomes and to investigate the factors associated with intervention outcomes. METHODS: An electronic database search was conducted using CINAHL, Medline, PsychINFO, Embase and the Cochrane Database of Systematic Reviews: 522 articles were identified for full text review and 15 studies were selected. The quality of studies were appraised and data were synthesised according to the review aims. RESULTS: Parent-only group interventions are effective in changing children's weight status, as well as other outcomes such as health behaviours and self-esteem, although these were reported inconsistently. Parent-only interventions were generally found to be similar to parent-child interventions, and minimal contact interventions but better than a waiting list control. Factors found to be associated with treatment outcomes, included session attendance, the child's age and weight at baseline, socioeconomic status of families and modification to the home food environment. The methodological quality of the studies included in the review was low, with only six studies rated to be methodologically adequate. CONCLUSIONS: Parent-only interventions may be an effective treatment for improving the health status of children and their families, particularly when compared with waitlist controls. However, results need to be interpreted with caution due to the low quality of the studies and the high rates of non-completion.

Association of physical activity, sedentary behavior, diet quality with adiposity: a longitudinal analysis in children categorized by baseline weight status.

BACKGROUND/OBJECTIVES: Childhood obesity rates have increased in recent years. The effectiveness of future public health interventions to reduce childhood obesity will be enhanced by a better understanding of behavioral factors that influence adiposity in children as they transition from childhood to adolescence. The purpose of this study was to examine whether initial weight status modifies the longitudinal associations of physical activity, sedentary behavior, and diet quality with changes in adiposity over time. SUBJECTS/METHODS: A total of 658 children (45% boys) were stratified into 3 groups based on 5th grade BMI percentiles ( < 85th, 85-95th, > 95th) and followed from 5th grade to 6th and/or 7th grade. Study variables, including fat-mass-index (FMI), moderate-to-vigorous physical activity (MVPA), diet quality, and sedentary behavior, were measured at 5th, 6th, and/or 7th grades. Separate growth curve models were conducted within each weight status group to examine the associations between MVPA, sedentary behavior, diet quality and adiposity, operationalized as FMI. All models controlled for sex, maturity offset, race, and parent education. RESULTS: Of the 658 children, 53% were classified with normal weight at baseline, 18% with overweight, and 29% with obesity. Associations between MVPA, sedentary behavior, diet quality and FMI varied within each weight status group. MVPA was negatively associated with adiposity (FMI) for all weight status groups. Diet quality and sedentary behavior were associated with adiposity only in children with obesity at baseline; neither diet quality nor sedentary behavior was associated with FMI for those with overweight. CONCLUSIONS: MVPA was negatively associated with adiposity (FMI) in all weight status groups, suggesting that MVPA may protect against higher adiposity. Sedentary behavior and diet quality were associated with adiposity only in children with obesity at baseline; neither sedentary behavior nor diet quality was associated with FMI for children with overweight.

Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children.

BACKGROUND/OBJECTIVES: Obesity polygenic risk scores (PRS) explain substantial variation in body mass index (BMI), yet associations between PRSs and appetitive traits in children remain unclear. To better understand pathways leading to pediatric obesity, this study aimed to assess the association of obesity PRSs and appetitive traits. SUBJECTS/METHODS: This study included 248 unrelated children aged 9-12 years. DNA from the children was genotyped (236 met quality control thresholds) and four weighted polygenic risk scores from previous studies were computed and standardized: a 97 SNP PRS, 266 SNP pediatric-specific PRS, 466 SNP adult-specific PRS, and ~2 million SNP PRS. Appetitive traits were assessed using a parent-completed Child Eating Behavior Questionnaire, which evaluated food approach/avoidance traits and a composite obesogenic appetite score. BMI was directly measured and standardized by age and sex. Three associations were evaluated with linear regression: (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits, the primary association of interest. RESULTS: Expected positive associations were observed between obesogenic appetitive traits and BMI and all four PRSs and BMI. Examining the association between PRSs and appetitive traits, all PRSs except for the 466 SNP adult PRS were significantly associated with the obesogenic appetite score. Each standard deviation increase in the 266 SNP pediatric PRS was associated with an adjusted 2.1% increase in obesogenic appetite score (95% CI: 0.6%, 3.7%, p = 0.006). Significant partial mediation of the PRS-BMI association by obesogenic appetite score was found for these PRSs; for example, 21.3% of the association between the 266 SNP pediatric PRS and BMI was explained by the obesogenic appetite score. CONCLUSIONS: Genetic obesity risk significantly predicted appetitive traits, which partially mediated the association between genetic obesity risk and BMI in children. These findings build a clearer picture of pathways leading to pediatric obesity.

Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

BACKGROUND/OBJECTIVES: Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. SUBJECTS: 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. METHODS: We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. RESULTS: The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. CONCLUSIONS: Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

Serum IL-36ß levels are associated with Insulin sensitivity in paediatric patients with obesity.

Although the orchestrating role of Interleukin-36 cytokines in regulating inflammation at barrier tissue sites, is well established, whether they play a significant role in the settings of metabolic health and disease, has yet to be fully established. Several recent studies have demonstrated that IL-36 cytokine expression is elevated among adult patients with obesity, and can play roles in regulating both insulin sensitivity and driving inflammation. In this report, we have extended these analyses to paediatric patients and identified an association between elevated serum levels of expression of the specific Interleukin-36 subfamily member, IL-36ß, among children with obesity displaying insulin sensitivity, compared to children with obesity who are insulin resistant. While these data further indicate a possible protective role for IL-36 in metabolic health, they also differ with previous findings from an adult patient cohort, where elevated levels of the related cytokine, IL-36γ, were found to occur in association with improved metabolic health. While highlighting important differences between paediatric and adult patient cohorts in the context of metabolic disease associated with obesity, these data underscore the need for a deeper mechanistic analysis of the role of IL-36 cytokines in disease.

Exposure to perfluoroalkyl and polyfluoroalkyl substances and pediatric obesity: a systematic review and meta-analysis.

INTRODUCTION: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are potentially obesogenic for children. We undertook a systematic review to synthesize this literature and explore sources of heterogeneity in previously published epidemiological studies. METHODS: Studies that collected individual-level PFAS and anthropometric data from children up to 12 years of age were identified by searching six databases. We excluded studies that only evaluated obesity measures at the time of birth. A full-text review and quality assessment of the studies was performed using the Office of Health Assessment and Translation (OHAT) criteria. Forest plots were created to summarize measures of association and assess heterogeneity across studies by chemical type and exposure timing. Funnel plots were used to assess small-study effects. RESULTS: We identified 24 studies, of which 19 used a cohort design. There were 13 studies included in the meta-analysis examining various chemicals and outcomes. Overall prenatal exposures to four different types of PFAS were not statistically associated with changes in body mass index (BMI) or waist circumference. In contrast, for three chemicals, postnatal exposures were inversely related to changes in BMI (i.e., per log10 increase in PFOS: BMI z-score of -0.16 (95% CI: -0.22, -0.10)). There was no substantial heterogeneity in the reported measures of association within prenatal and postnatal subgroups. We observed modest small-study effects, but correction for these effects using the Trim and Fill method did not change our summary estimate(s). CONCLUSION: Our review found no evidence of a positive association between prenatal PFAS exposure and pediatric obesity, whereas an inverse association was found for postnatal exposure. These findings should be interpreted cautiously due to the small number of studies. Future research that can inform on the effects of exposure mixtures, the timing of the exposure, outcome measures, and the shape of the exposure-response curve is needed.

Improved walking energy efficiency might persist in presence of simulated full weight regain after multidisciplinary weight loss in adolescents with obesity: the POWELL study.

AIM: Weight loss leads to a reduction of the energy cost of walking but the respective implications of the metabolic and mechanic changes remain unknown. The present study compares the post-weight loss energy cost of walking (Cw) with and without a total reload of the induced weight reduction in adolescents with obesity. METHODS: Energy cost of walking and substrate use were evaluated during a graded walking exercise (4×6-min at 0.75, 1, 1.25, 1.5 m.s-1) before (V1) and after a 12-week intervention in 21 adolescents with obesity (11 girls; 13.8 ± 1.4 y). After weight loss, the walking exercise was randomly repeated once without weight reload (V2) and once with a loading corresponding to the total induced weight loss during the program (V2L). Body composition was assessed before and after the intervention. RESULTS: Body weight and fat mass decreased in response to the 12-week intervention (p < 0.001), while FFM did not change. The absolute gross Cw (ml.m-1) was higher on V1 compared with V2 at every speed. The absolute net Cw (ml.m-1) was higher on V1 compared to V2L at 0.75 m.s-1 (p = 0.04) and 1 m.s-1 (p = 0.02) and higher on V2L compared with V2 at 1.5 m.s-1 (p = 0.03). Net Cw (ml.m-1.kg-1) on V1 being higher than V2 (p < 0.001), and V2L higher than V2 (p = 0.006). The absolute CHO oxidation (mg.min-1) did not show any condition effect (p = 0.12) while fat utilization was higher on V1 compared to V2 and V2L (p < 0.001). Relative to body weight CHO oxidation was lower on V1 compared to V2 (p = 0.04) and V2L (p = 0.004) while relative to body weight fat oxidation was higher on V1 than V2 (p = 0.002). CONCLUSION: Adolescents with obesity might not show an entire rise back to pre-weight loss values of their metabolic cost of walking when weight gain is simulated. These new findings suggest metabolic and physiological adaptations to weight loss of the energy metabolism that remain to be clarified.

Maternal gestational diabetes and childhood adiposity risk from 6 to 8 years of age.

BACKGROUND/OBJECTIVE: Previous studies found conflicting results on the association between maternal gestational diabetes mellitus (GDM) and childhood overweight/obesity. This study was to assess the association between maternal GDM and offspring's adiposity risk from 6 to 8 years of age. METHODS: The present study longitudinally followed 1156 mother-child pairs (578 GDM and 578 non-GDM) at 5.9 ± 1.2 years postpartum and retained 912 mother-child pairs (486 GDM and 426 non-GDM) at 8.3 ± 1.6 years postpartum. Childhood body mass index (BMI), waist circumference, body fat and skinfold were measured using standardized methods. RESULTS: Compared with the counterparts born to mothers with normal glucose during pregnancy, children born to mothers with GDM during pregnancy had higher mean values of adiposity indicators (waist circumference, body fat, subscapular skinfold and suprailiac skinfold) at 5.9 and 8.3 years of age. There was a positive association of maternal GDM with changes of childhood adiposity indicators from the 5.9-year to 8.3-year visit, and ß values were significantly larger than zero: +0.10 (95% CI: 0.02-0.18) for z score of BMI for age, +1.46 (95% CI: 0.70-2.22) cm for waist circumference, +1.78% (95% CI: 1.16%-2.40%) for body fat, +2.40 (95% CI: 1.78-3.01) mm for triceps skinfold, +1.59 (95% CI: 1.10-2.09) mm for subscapular skinfold, and +2.03 (95% CI: 1.35-2.71) mm for suprailiac skinfold, respectively. Maternal GDM was associated with higher risks of childhood overweight/obesity, central obesity, and high body fat (Odd ratios 1.41-1.57 at 5.9 years of age and 1.73-2.03 at 8.3 years of age) compared with the children of mothers without GDM. CONCLUSIONS: Maternal GDM was a risk factor of childhood overweight/obesity at both 5.9 and 8.3 years of age, which was independent from several important confounders including maternal pre-pregnancy BMI, gestational weight gain, children's birth weight and lifestyle factors. This significant and positive association became stronger with age.

Left atrial remodeling in adolescents with obesity evaluated by speckle-tracking echocardiography.

BACKGROUND AND AIMS: In adolescents with obesity, a left atrial (LA) enlargement has been reported. However, data regarding its function and its stiffness are missing. The aim of this study was to describe LA morphology and function, using speckle-tracking echocardiography (STE) and to explore their potential determinants in adolescents with obesity. METHODS: Twenty-eight adolescent women with obesity (13.2 ± 1.4 yr) with an illness duration of 130 ± 27 months and 33 controls (14.1 ± 2.0 yr) underwent a resting echocardiography including an analysis of left ventricular (LV) and LA morphologies and strains. A fasting venous blood sample was performed to biochemical determinations including inflammation markers. RESULTS: LA volume and stiffness index were increased in adolescents with obesity compared to controls. LA reservoir, conduit and booster pump functions were not different between groups. By stepwise forward multivariate regression analyses, systolic blood pressures, cardiac output and sedimentation rate were the independent determinants of LA volume (p < 0.0001, ß-coefficient = 0.460) whereas only the body mass index was an independent determinant of LA stiffness (p = 0.003, ß-coefficient = 0.413). CONCLUSION: In adolescents with obesity, we observed a specific LA remodeling, including higher volume and lower stiffness, which could constitute early signs of an altered LV diastolic function.