Early Life Obesity Research Articles

Epigenetic programming of obesity in early life through modulation of the kynurenine pathway.

Childhood obesity is a global health concern that has its origins before birth. Although genetics plays a crucial role, increasing evidence suggests that epigenetic modifications during fetal life could also influence its incidence. In this model, during the fetal period, interactions between genetic makeup, intrauterine factors, and environmental conditions, increase the risk of childhood obesity. This is in accordance with the Developmental Origins of Health and Disease (DOHaD) hypothesis, in which specific intrauterine environments can have long-lasting effects on the immune system's essential functions during crucial stages of fetal growth, resulting in permanent changes to the immune function of the offspring. Consequently, dysfunction can consequently make the offspring more prone to inflammatory and immune-related disorders later in life. In this review, we examine how maternal inflammation could influence the risk of childhood obesity. We propose that during pregnancy, modification of the expression of critical genes in metabolic and signaling pathways, such as the kynurenine (Kyn) pathway, occurs due to increased levels of maternal inflammation. We also propose that such expression differences are mediated by epigenetic changes. Furthermore, we also hypothesize that the Kyn pathway produces metabolites that have immunoregulatory effects and may play a crucial role in regulating inflammation during pregnancy. As a result, interventions aimed at improving maternal inflammation may be able to help alleviate the risk of childhood obesity.

A Systematic Review of Early General Parenting Interventions: Long-term Effects in Underrepresented Populations and Implications for Obesity Prevention.

While some parenting interventions designed for early-life obesity prevention have demonstrated short-term success, there is limited evidence of longer-term impacts and feasibility with underrepresented populations. The goal of this review was to examine existing general parenting programs for parents of children 0-5years that were not designed to target obesity but investigated long-term effects on parenting and/or were conducted with underrepresented populations to offer recommendations for the modification or development of parenting-focused obesity prevention programs. Most studies with sustained impacts on parenting in underrepresented populations were brief, group-based programs for parents of children 2-5years. Many effective interventions included guided practice of skills and cultural adaptations. Unique intervention approaches included remote or school-based delivery models and motivational interviewing. Brief, group-based programs for parents of young children may be a promising approach to achieving longer-term impacts of parenting interventions on obesity risk among underrepresented populations.

Abstract P351: Obesity in Early Life Leads to Endothelial and Erectile Dysfunction in Young Adult Rats.

Background: Erectile dysfunction (ED) is largely associated with obesity, however, the consequences of early life obesity for ED in young adulthood are unknown. We hypothesize that obesity induced by preweaning overfeeding impairs vascular and erectile function and affects blood pressure in young adult male rats (5-month-old). Methods: At postnatal day (PND) 1, Wistar rats were divided into a normal litter (NL, 5 female + 5 male pups/dam) or small litter (SL, 2 male + 1 female pup/dam) during lactation. After weaning, SL pups had increased body weight. Next, rats from both groups returned to normal size colonies (4-5 rats per cage) and were fed standard chow. At PND160, we evaluated body weight and fat pad deposition, mean arterial pressure (MAP) by tail-cuff, and pudendal artery (PA) and corpus cavernosum (CC) reactivity. Concentration-response curves to phenylephrine (PE) or acetylcholine (ACh) were performed in both preparations. In the CC, contraction and relaxation to electrical field stimulation (EFS) were obtained. Concentration-response curves were analyzed using non-linear regression analysis. RNA sequencing (RNAseq) analyses were performed in both PA and CC. Data were analyzed by Student’s t-test and presented as mean ± S.E.M. Statistical significance was set at p<0.05. Results: At PND160 no differences in body weight were observed in SL (594±14g) compared to NL (559±13g), however, there was an increase in fat deposition in SL (retroperitoneal fat: NL 7.47±0.69g vs SL 11.25±1.23g; perigonadal fat: NL 10.05±0.55g vs SL 13.24±1.16g). MAP was higher in SL (120.5±1.20 mmHg vs 114.9±0.58 NL). In the PA, ACh-induced relaxation was reduced in SL (Emax: 28±6%) vs NL (Emax: 68±5.5%), with no changes in the contraction to PE. In the CC, EFS-induced relaxation was significantly decreased in SL rats compared to NL rats (16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). RNAseq revealed that, in PA from SL rats, 289 and 224 genes were down and upregulated, respectively, while in the CC from SL rats, 115 genes were downregulated, and 110 genes were upregulated. Among them, hcn2 gene (which encodes HCN2, the hyperpolarization-activated cyclic nucleotide-gated potassium and sodium channel 2) was strongly downregulated in both PA and CC, and this may affect mechanotransduction. Conclusion: Our data shows that early-life obesity causes long-lasting vascular and cavernous damage that might be associated with endothelial and erectile dysfunction in young adulthood.

Mendelian randomization analysis separated the independent impact of childhood obesity and adult obesity on socioeconomic status, psychological status, and substance use

BackgroundObesity is linked to a variety of psychosocial and behavioral outcomes but the causalities remain unclear yet. Determining the causalities and distinguishing between the separate effects of childhood and adult obesity is critical to develop more targeted strategies to prevent adverse outcomes. MethodsWith single nucleotide polymorphisms (SNPs) used as genetic variables, we employed univariable Mendelian randomization (UVMR) to explore the causalities between childhood and adult body mass index (BMI) and socioeconomic status, psychological status, and substance use. Genetic data for childhood and adult BMI came respectively from 47,541 children aged 10 years and 339,224 adult participants. The outcome data were obtained from corresponding consortia. The direct impact of childhood BMI and adult BMI was then examined using a multivariable MR (MVMR). ResultsUVMR found that higher childhood BMI was linked causally to lower household income (β = −0.06, 95 % CI = −0.08 ∼ −0.03, P = 4.86 × 10−5), decreased subjective well-being (β = −0.07, 95 % CI = −0.12 ∼ −0.03, P = 1.74 × 10−3), and an increased tendency of smoking regularly (OR = 1.12, 95 % CI = 1.04–1.20, P = 1.52 × 10−3). Similar results were observed in adult BMI. MVMR further revealed that after adjusting with adult BMI, childhood BMI remained an isolated impact on household income. The impacts of adult BMI on the outcomes were diminished when adjusting with childhood BMI. ConclusionThe findings indicate the impacts of childhood obesity on subjective well-being and smoking initiation are a result of higher BMI sustaining into adulthood, whereas the effect on household income is attributed to a lasting impact of obesity in early life. The results would help facilitate more targeted strategies for obesity management to prevent adverse outcomes.

Associations of Maternal Breastmilk microRNAs and Infant Obesity Status at 1 Year.

Infant consumption of human milk (HM) is associated with a reduced risk of overweight and obesity, but the reasons for this relationship are not completely understood. There is emerging evidence that micro RNAs (miRNAs) regulate infant development and metabolism, but the associations between HM miRNAs and infant growth remain poorly understood. We examined the relationship between HM miRNA consumption and infant obesity in 163 mother-infant dyads to determine (1) if miRNA profiles differentiate infants with obesity, and (2) if individual miRNAs accurately predicted infant obesity status at one year of age. Infant obesity was categorized as weight-for-length (WFL) Z scores or conditional weight gain (CWG) in the 95th percentile. HM miRNA profile was associated with infant age (r2 = 6.4%, p = 0.001), but not maternal obesity status (r2 = 1.5%, p = 0.87) or infant weight status (WFL Z-score) at birth (r2 = 0.6%, p = 0.4), 1 month (r2 = 0.5%, p = 0.6), or 4 months (r2 = 0.8%, p = 0.2). Nine HM miRNAs were associated with either 12-month CWG or 12-month WFL Z scores. Among these 9 miRNAs, miR-224-5p remained significant in a logistic regression model that accounted for additional demographic factors (estimate = -27.57, p = 0.004). These findings suggest involvement of HM miRNAs and particularly miR-224-5p in infant growth, warranting further investigation. To our knowledge, this is the largest study of HM miRNAs and early-life obesity and contributes to the understanding of the relationship between HM miRNAs and infant growth.

Association Between Early-Life Exposure to Antibiotics and Development of Child Obesity: Population-Based Study in Italy.

Childhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity. This study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life. An Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12, and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, and ≥3 prescriptions). Obesity was defined as a BMI z score >3 for children aged ≤5 years and >2 for children aged >5 years, using the World Health Organization growth references. The obese incidence rate (IR) × 100 person-years and the relative 95% CI were computed using infant sex, area of residence, preschool and school age, and area deprivation index, which are the covariates of interest. A mixed-effect Cox proportional hazards model was used to estimate the hazard ratio and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months and 14 years of age, considering the family pediatricians as a random factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results. Among 121,540 children identified, 54,698 were prescribed at least an antibiotic within the first year of life and 26,990 were classified as obese during follow-up with an incidence rate of 4.05 cases (95% CI 4.01-4.10) × 100 person-year. The risk of obesity remained consistent across different timings of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted hazard ratio [aHR] 1.07, 95% CI 1.04-1.10; aHR 1.06, 95% CI 1.03-1.09; and aHR 1.07, 95% CI 1.04-1.10, respectively). Increasing the number of antibiotic exposures increases the risk of obesity significantly (P trend<.001). The individual-specific age analysis showed that starting antibiotic therapy very early (between 0 and 5 months) had the greatest impact (aHR 1.12, 95% CI 1.08-1.17) on childhood obesity with respect to what was observed among those who were first prescribed antibiotics after the fifth month of life. These results were consistent across subgroup and sensitivity analyses. The results from this large population-based study support the association between early exposure to antibiotics and an increased risk of childhood obesity. This association becomes progressively stronger with both increasing numbers of antibiotic prescriptions and younger age at the time of the first prescription.

Pre-Weaning Overfeeding Promotes Prepubertal Obesity and Evokes Sexual Dysfunction in Young Adult Rats

Obesity in early life can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol, and these conditions are associated with sexual dysfunction. Here, we hypothesized that pre-weaning overfeeding can have long lasting effects on body fat distribution and erectile function that will be observed in young adult males. On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. Following euthanasia at PND 120, the corpus cavernosum (CC) was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p&lt;0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g/100g, p&lt;0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g/100g, p&lt;0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534.2.7±13 vs. SL 631.6±10, g, p&lt;0.05), retroperitoneal (NL 1.31±0.11 vs. SL 1.82±0.14, g/100g, p&lt;0.05) and perigonadal (NL 1.74±0.10 vs. SL 2.18±0.15, g/100g, p&lt;0.05) adipose tissue when compared with NL group. The CC of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs. SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs. SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs. SL 3 ± 0.4 mN), whereas the relaxation was decreased in SL (1 Hz: NL 0.77 ± 0.18% vs. SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs. SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs. SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs. SL 4.9±0.7, mN, p=0.1) in the CC of SL. Incubation with indomethacin (10μM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Moreover, the CC of SL rats presented increased expression of Phospho-p44/42 MAPK (NL 0.9±0.25 vs. SL 1.3±0.11, p=0.2). Finally, proteome profiler cytokine array of serum samples from SL animals showed increased circulating levels of cytokines and chemokines associated with obesity, aging, and vascular dysfunction. Together, these data suggest that early prepubertal obesity has long-lasting negative implications on sexual function in young adulthood. National Institutes of Health (NIH); American Heart Association (AHA); Fulbright Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 2197: Weight history and colorectal cancer risk in the Cancer Prevention Study-3 cohort

Abstract While the link between obesity and colorectal carcinogenesis is established, limited evidence suggests that early-life overweight/obesity may be an important consideration, particularly in the development of early-onset colorectal cancer (CRC). Using data from the American Cancer Society’s Cancer Prevention Study-3 (CPS-3), we investigated the association of body weight across the life course and risk of CRC. From 2006-13, over 300,000 participants (ages 30-65) enrolled in the CPS-3 cohort and provided a baseline waist circumference (WC) measure, self-reported baseline weight and height, weight at age 18, and weight at each decade of adulthood (20s to current age). Body shape phenotype (apple, pear, other) was self-reported in 2015. Excess body mass index (BMI)-years was calculated by subtracting a reference BMI of 25 from the reported BMI for each decade of life and aggregating excess BMI for the reported years of life. Through 2018, 424 incident cases of colorectal cancer were reported, of which 94 were younger than 50 years. Associations of BMI measures and WC with incident CRC were estimated using multivariable-adjusted Cox proportional hazards regression and stratified by sex and body shape. After exclusions (n=248,804), 78% of participants were women, 85% were non-Hispanic white, 69% were never smokers, and 8% had a family history of CRC. The mean baseline age was 47.8 (women) and 48.5 (men) years. The mean baseline BMI, WC, and age 18 BMI were 27.6 kg/m2, 91.9 cm, and 21.7 kg/m2, respectively, among women and 28.3 kg/m2, 103.8 cm, and 23.1 kg/m2, respectively, among men. Baseline BMI was associated with 8% higher CRC risk (95% confidence interval (CI) 0.99-1.18) per 5 kg/m2 increase. However, apple body shape was associated with higher CRC risk (hazard ratio (HR) per 5 kg/m2 BMI = 1.18, 95% CI 1.02-1.38). WC was associated with higher CRC risk (HR 1.08, 95% CI 1.01-1.15) per 10 cm increase, and the association was higher for apple body shape (HR 1.14, 95% CI 1.01-1.28). BMI at age 18 was associated with 17% higher CRC risk (95% CI 1.03-1.32) per 5 kg/m2 increase, and the association was higher for apple body shape (HR 1.36, 95% CI 1.12-1.65). Associations for non-apple body shapes were not statistically significant across all exposures. For early-onset CRC, associations with baseline BMI, WC, and age 18 BMI were suggestive of higher risk but not statistically significant. Participants in the highest category of excess BMI-years (women ≥35, men ≥81) relative to those in the lowest had 56% higher risk of overall CRC (95% CI 1.19-2.05), but the association with early-onset CRC was not statistically significant (HR 1.92, 95% CI 0.90-4.07). These findings suggest that while obesity is associated with higher CRC risk, excess weight gain around the waist and at younger ages may be of importance. Studies are needed to confirm these findings and further investigate the potential role of early-life obesity in the development of early-onset CRC. Citation Format: Caroline Y. Um, Christina C. Newton, Aparna Parikh, Marjorie L. McCullough, Alpa V. Patel. Weight history and colorectal cancer risk in the Cancer Prevention Study-3 cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2197.

Overview: Global burden of liver disease

About 2 million deaths occur annually, and 4% of all deaths are caused by liver disease, which ranks as the 11 leading cause of death worldwide. This review includes the different kinds of liver disorders and their global prevalence. It focuses primarily on areas where significant new data is available, such as drug-induced liver injury, acute chronic liver disease, hepatocellular carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, and viral hepatitis. Most deaths are attributed to complications arising from hepatocellular carcinoma and cirrhosis. Obesity in Early life is an independent risk factor for cancer and cirrhosis. In the western world, alcohol is the primary cause of liver cirrhosis. It also covers some special considerations, such as hepatic conditions during COVID-19 and pregnancy, with a retrospective study. Additionally, we cover important data on sign symptoms, prevention, diagnosis with specialized techniques, and treatment with various drugs.

Early life adversity and obesity risk in adolescence: a 9-year population-based prospective cohort study.

There are few prospective studies of factors that mediate the association between exposure to adverse childhood experiences (ACEs) and obesity in adolescence. Our aim was to address this limitation. We used prospective data from the Growing up in Ireland cohort study, with measurements at 9, 13, and 18 years old. The exposures were 14 adverse experiences before age 9. The mainoutcome was body mass index (BMI) at 18 years. Mediators were daily activity, diet quality, self-image and behavioural difficulties at 13 years. Among the 4561 adolescentsin the final cohort, 77.2% experienced any adversity, 50.5% were female and 26.7% were overweight/obese at 18 years. BMI Z was higher at ages 9 (0.54 vs 0.43, p < 0.05, 95% CI of difference: -0.22, -0.01) and 13 years (0.50 vs 0.35, p < 0.05, 95% CI of difference: -0.25, -0.06), in those exposed to an ACE, compared to those unexposed. Structural equation models revealed that behavioural difficulties (β = 0.01; 95% CI: 0.007-0.018, p < 0.001) and self-concept (β = 0.0027; 95% CI: 0.0004-0.0050, p = 0.026) indirectly mediate the association between exposure to ACEs and BMI at 18 years. The association between ACEs and BMI in adolescence is mediated by behavioural difficulties and self-concept. In a previous study, we found modest associations between exposure to a range of adverse childhood experiences and weight gain at 13 years of age. The strength of the association between adverse childhood experiences and weight gain was lower at 18 years of age compared to the association observed at 13 years and was no longer significant after controlling for confounding and including possible mediators. The association between adverse childhood experiences and BMI in adolescence is indirectlymediated by behavioural difficulties and self-concept.

The risk prediction of intergenerational transmission of overweight and obesity between mothers and infants during pregnancy.

Overweight and obesity in mothers before pregnancy lead to overweight and obesity in their offspring, which is the main form of intergenerational transmission of overweight and obesity in early life. Many factors, especially non-genetic factors, may influence intergenerational transmission, but little prediction research has been conducted. Therefore, we analyzed the status of intergenerational transmission in maternal and infant overweight and obesity. Second, we explored the factors during the pregnancy that might affect the the intergenerational transmission; According to the two application scenarios of pregnancy screen and self-management, risk prediction models for pregnant women were carried out. Based on a prospective birth cohort, a total of 908 mothers and offspring were followed up during early life. Follow-up visits were performed at the first trimester, second trimester, third trimester, delivery, 42 days after delivery, and 6 months and 12 months of age. The investigation methods included questionnaire survey, physical examination, biological sample collection and clinical data collection. In terms of risk prediction, univariate analysis was used to screen candidate predictors. Second, multivariable Cox proportional hazard regression models were used to determine the final selected predictors. Third, the corresponding histogram models were drawn, and then the 10-fold cross-validation methods were used for internal verification. Regarding intergenerational transmission of overweight and obesity between mothers and infants during pregnancy, the risk prediction model for pregnancy screen was constructed. The model established: h(t|X) = h0(t)exp.(- 0.95 × (Bachelor Degree or above) + 0.75 × (Fasting blood glucose in the second trimester) + 0.89 × (Blood pressure in the third trimester) + 0.80 × (Cholesterol in third trimester) + 0.55 × (Abdominal circumference in third trimester))., with good discrimination (AUC = 0.82) and calibration (Hosmer-Lemeshow2 = 4.17). The risk prediction model for self-management was constructed. The model established: h(t|X) = h0(t)exp. (0.98 × (Sedentary >18METs) + 0.88 × (Sleep index≥8) + 0.81 × (Unhealthy eating patterns Q3/Q4) + 0.90 × (Unhealthy eating patterns Q4/Q4) + 0.85 × (Depression)), with good discrimination (AUC = 0.75) and calibration (Hosmer-Lemeshow2 = 3.81). The risk predictions of intergenerational transmission of overweight and obesity between mothers and infants were performed for two populations and two application scenarios (pregnancy screening and home self-management). Further research needs to focus on infants and long-term risk prediction models.

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

Historical Obesity and Early-Onset Cancers: A Propensity-Weighted Analysis of the National Health and Nutrition Examination Survey.

The incidence of early-onset obesity-related cancers (diagnosed < 50years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity. We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups. After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30kg/m2) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1kg/m2, p < 0.0001), with a trend towards a higher BMI before 19years old. Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity.

Specific features of endocrine regulation of plastic processes in premature infants and children small for gestational age

Low-birthweight and preterm infants have high risk of obesity and obesity-related diseases in the future. This review article identifies risk factors and endocrine biomarkers with greatest predictive value to the metabolic diseases development. Low concentrations of IGF-1 in low-birthweight children are associated with adipogenesis. Low leptin levels may be considered as a biomarker of catch-up growth. Long term programming effects of in utero exposure to leptin extend beyond infancy into early childhood. Adiponectin levels are positively correlated with obesity in early life, but not at ages older than three years. Rapid postnatal growth rate is associated with metabolic syndrome. Conclusion. Specific features of endocrine regulation of growth and dynamics of plastic processes in premature infants and SGA children are associated with excessive accumulation of adipose tissue, which can function as a mechanism for metabolic programming of distant endocrine and cardiometabolic disorders.

Association between childhood obesity and infertility in later life: a systematic review of cohort studies

BackgroundThe global prevalence of childhood obesity has exhibited a troubling surge in recent years. Due to the raised questions regarding its potential correlation with infertility in adulthood, this systematic review has been undertaken to explore the relationships between childhood obesity, and infertility later in life.MethodsA comprehensive search was performed in three international databases (PubMed, Web of Science, and Scopus). All cohort (retrospective or prospective), case-cohort, and nested case-control studies until April 2022 which assessed the association of obesity in children and adolescents with male and female infertility indicators in later life were included. The quality of the included studies was assessed by Newcastle-Ottawa quality assessment checklists.ResultOut of the initial 32,501 documents, eleven eligible studies with a total sample size of 498,980 participants were included. Five studies focused on the number of offspring and indicated that obesity, especially in adolescence had an association with later life lower number of children, nulliparity, and childlessness in both men and women. Concerning conceiving problems, two studies showed that obesity before age 12 increased the risk of female fertility problems in the future. Two studies reported that obesity in early life raised the risk of impaired female reproductive system such as menstrual or ovulatory problems. As well as females, a study discovered that obesity in men during their 20s was linked to an elevated risk of low sperm motility and poor sperm morphology. Another study has reported men with higher pre-pubertal BMI had lower sex hormone-binding globulin; however, the same association was not seen between childhood BMI and semen quality.ConclusionThe evidence suggests a positive association between childhood obesity with infertility indicators in later life. Childhood weight reduction strategies are suggested to be implemented in societies in order to reduce infertility rates in later life.

Behavioural susceptibility theory: the role of appetite in genetic susceptibility to obesity in early life.

Excess weight gained during the early years and, in particular, rapid weight gain in the first 2 years of life, are a major risk factors for adult obesity. The growing consensus is that childhood obesity develops from a complex interaction between genetic susceptibility and exposure to an 'obesogenic' environment. Behavioural susceptibility theory (BST) was developed to explain the nature of this gene-environment interaction, and why the 'obesogenic' environment does not affect all children equally. It hypothesizes that inherited variation in appetite, which is present from birth, determines why some infants and children overeat, and others do not, in response to environmental opportunity. That is, those who inherit genetic variants promoting an avid appetite are vulnerable to overeating and developing obesity, while those who are genetically predisposed to have a smaller appetite and lower interest in food are protected from obesity-or even at risk of being underweight. We review the breadth of research to-date that has contributed to the evidence base for BST, focusing on early life, and discuss implications and future directions for research and theory. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Human-centered designed communication tools for obesity prevention in early life

ObjectiveHow we communicate about obesity is critical as treatment paradigms shift upstream. We previously identified parental perceptions, concerns, beliefs, and communication preferences about early life obesity risk. We engaged parents of children 0 to 24 months of age and pediatricians from Indianapolis, Indiana, USA in the co-design of messages and tools that can be used to facilitate parent/provider conversations about early life obesity prevention. MethodsFrom April to June 2021, we conducted a series of co-design workshops with parents of children ages 0 to 24 months and pediatricians to identify their preferences for communicating obesity prevention in the setting of a pediatric well visit. Human-centered design techniques, including affinity diagraming and model building, were used to inform key elements of a communication model and communication strategy messages. These elements were combined and refined to create prototype tools that were subsequently refined using stakeholder feedback. ResultsParent participants included 11 mothers and 2 fathers: 8 white, 4 black, and 1 Asian; median age 33 years with 38% reporting annual household incomes less than $50,000. Pediatricians included 7 female and 6 male providers; 69% white. Through an iterative process of co-design, we created an exam room poster that addresses common misconceptions about infant feeding, sleep and exercise, and a behavior change plan to foster parent/provider collaboration focused on achieving children’s healthy weight. ConclusionsOur hands-on, collaborative approach may ultimately improve uptake, acceptability and usability of early life obesity interventions by ensuring that parents remain at the center of prevention efforts.

Associations between cord blood metabolic factors and early-childhood growth and overweight and obesity.

This prospective cohort study was aimed at investigating the associations between cord blood metabolic factors and early-childhood growth, further elucidating the relationships between cord blood metabolites and overweight and obesity in early life. A total of 2,267 pairs of mothers and offspring were recruited in our study. Cord blood plasma was assayed for triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), C-peptide, insulin, and glycosylated hemoglobin type A1C (HbA1c) levels. Data of anthropometric measurements were collected from offspring at birth, 6 months, 12 months, and 18 months. Multiple linear regression models were used to evaluate the correlations between cord blood metabolic factors and weight Z-scores, body mass index (BMI) Z-scores, and weight gains at the early stage of life. Forward stepwise logistic regression analyses were applied to explore the associations between cord blood metabolic factors and early-childhood overweight and obesity. Receiver operating characteristic (ROC) curve analyses were applied to determine the optimal cutoff points for cord blood metabolic factors in predicting early-childhood overweight and obesity. After adjustments for covariates, cord blood TG concentrations and TG/TC ratios were negatively associated with weight Z-scores from birth to 18 months. Cord blood C-peptide and HbA1c levels were inversely associated with weight Z-scores at 6 months and 18 months. Cord blood TG concentrations and TG/TC ratios were negatively correlated with BMI Z-scores up to 18 months. Cord blood C-peptide levels and HbA1c levels were inversely correlated with BMI Z-scores at 18 months. Cord blood TG, TG/TC ratios, C-peptide, and HbA1c had negative correlations with weight gains from birth to 6 months, but the correlations attenuated as time went on. Increase in cord blood TG and HbA1c levels and TG/TC ratios were significantly associated with decreased risks of overweight and obesity at 6 months, 12 months, and 18 months. Cord blood metabolic factors were significantly associated with early-childhood growth patterns.

Socio-Demographic, Lifestyle, and Clinical Characteristics of Early and Later Weight Status in Older Adults: Secondary Analysis of the ASPREE Trial and ALSOP Sub-Study.

To identify the socio-demographic, lifestyle, and clinical characteristics associated with self-reported weight status in early (age 18 years) and late (age ≥ 70 years) adulthood. The number of participants was 11,288, who were relatively healthy community-dwelling Australian adults aged ≥70 years (mean age 75.1 ± 4.2 years) in the Aspirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) sub-study. Self-reported weight at the study baseline (age ≥ 70 years) and recalled weight at age 18 years were collected. Height measured at baseline was used to calculate the BMI at both time points. Individuals were categorised into one of five 'lifetime' weight status groups: healthy weight (at both age 18 year and ≥70 years), overweight (at either or both times), non-obese (age 18 year) to obesity (age ≥70 years), obesity (age 18 years) to non-obese (age ≥ 70 years), and early and later life obesity (at age 18 years and ≥70 years). Participants who experienced obesity in early and/or late adulthood were at a higher risk of adverse clinical characteristics. Obesity in late adulthood (regardless of early adulthood weight status) was associated with high proportions of hypertension, diabetes, and dyslipidaemia, whereas obesity in early adulthood (regardless of late adulthood weight status) was associated with lower cognitive scores (on all four measures). Healthy or overweight weight status in early and later adulthood was associated with more favourable socioeconomic, lifestyle, and clinical measures. Obesity in early adulthood was associated with lower cognitive function in later adulthood, whereas obesity in later adulthood was associated with hypertension, diabetes, and dyslipidaemia.

Early Life Obesity Increases Neuroinflammation, Amyloid Beta Deposition, and Cognitive Decline in a Mouse Model of Alzheimer's Disease.

Obesity, a known risk factor of Alzheimer's disease (AD), increases the activation of microglia, leading to a proinflammatory phenotype. Our previous work shows that a high fat diet (HFD) can cause neuroinflammation and cognitive decline in mice. We hypothesized that proinflammatory activation of brain microglia in obesity exacerbates AD pathology and increases the accumulation of amyloid beta (Aβ) plaques. Presently, we tested cognitive function in 8-month-old male and female APP/PS1 mice fed a HFD, starting at 1.5 months of age. Locomotor activity, anxiety-like behavior, behavioral despair, and spatial memory were all assessed through behavioral tests. Microgliosis and Aβ deposition were measured in multiple brain regions through immunohistochemical analysis. Our results show that a HFD decreases locomotor activity, while increasing anxiety-like behavior and behavioral despair independent of genotype. A HFD led to increased memory deficits in both sexes, with HFD-fed APP/PS1 mice performing the worst out of all groups. Immunohistochemical analysis showed increased microgliosis in mice fed a HFD. This was accompanied by an increase in Aβ deposition in the HFD-fed APP/PS1 mice. Together, our results support that HFD-induced obesity exacerbates neuroinflammation and Aβ deposition in a young adult AD mouse model, leading to increased memory deficits and cognitive decline in both sexes.