Accelerated Weight Gain Research Articles

Weight tracking in childhood and adolescence and type 2 diabetes risk.

The aim of this work was to examine the associations of average weight and weight velocity in three growth periods from birth through adolescence with type 2 diabetes incidence. Child participants were selected from a 43year longitudinal study of American Indians to represent three growth periods: pre-adolescence (birth to ~8years); early adolescence (~8 to ~13years); and late adolescence (~13 to ~18years). Age-, sex- and height-standardised weight z score mean and weight z score velocity (change/year) were computed for each period. Participants were followed for up to 25years from the end of each growth period until they developed diabetes. Associations of weight z score mean or weight z score velocity with diabetes incidence were determined with sex-, birth date- and maternal diabetes-adjusted Poisson regression models. Among 2100 participants representing the pre-adolescence growth period, 1558 representing the early adolescence period and 1418 representing the late adolescence period, there were 290, 315 and 380 incident diabetes cases, respectively. During the first 10years of follow-up, the diabetes incidence rate ratio (95% CI) was 1.72 (1.40, 2.11)/SD of log10 weight z score mean in pre-adolescence, 2.09 (1.68, 2.60)/SD of log10 weight z score mean in early adolescence and 1.85 (1.58, 2.17)/SD of log10 weight z score mean in late adolescence. The diabetes incidence rate ratio (95% CI) was 1.79 (1.49, 2.17)/SD of log10 weight z score velocity in pre-adolescence, 1.13 (0.91, 1.41)/SD of log10 weight z score velocity in early adolescence and 1.29 (1.09, 1.51)/SD of log10 weight z score velocity in late adolescence. There were strong correlations in the weight z score means and weak correlations in the weight z score velocities between successive periods. Higher weight and accelerated weight gain in all growth periods associate with increased type 2 diabetes risk. Importantly, higher weight and greater weight velocity during pre-adolescence jointly associate with the highest type 2 diabetes risk. Graphical abstract.

Post-traumatic stress disorder and the association with overweight, obesity, and weight change among individuals exposed to the World Trade Center disaster, 2003–2016

Among Veterans, post-traumatic stress disorder (PTSD) has been shown to be associated with obesity and accelerated weight gain. Less is known among the general population. We sought to determine the impact of PTSD on body mass index (BMI) and weight change among individuals with exposure to the World Trade Center (WTC) disaster. We examined individuals from the WTC Health Registry. PTSD symptoms were assessed on multiple surveys (Waves 1-4) using the PTSD Checklist-Specific. Three categories of post-9/11 PTSD were derived: no, intermittent, and persistent. We examined two outcomes: (1) Wave 3 BMI (normal, overweight, and obese) and (2) weight change between Waves 3 and 4. We used multivariable logistic regression to assess the association between PTSD and BMI (N = 34 958) and generalized estimating equations to assess the impact of PTSD on weight change (N = 26 532). Sex- and age-stratified analyses were adjusted for a priori confounders. At Wave 3, the observed prevalence of obesity was highest among the persistent (39.5%) and intermittent PTSD (36.6%) groups, compared to the no PTSD group (29.3%). In adjusted models, persistent and intermittent PTSD were consistently associated with a higher odds of obesity. Weight gain was similar across all groups, but those with persistent and intermittent PTSD had higher estimated group-specific mean weights across time. Our findings that those with a history of PTSD post-9/11 were more likely to have obesity is consistent with existing literature. These findings reaffirm the need for an interdisciplinary focus on physical and mental health to improve health outcomes.

Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

The purpose of this systematic review and meta-analysis of the literature was to analyze and evaluate the impact of prematurity and accelerated weight gain on the risk of childhood and adolescent obesity. CINAHL, Embase, PubMed, and Web of Science databases were searched until December 2019 which yielded 19 studies with a total of 169,439 children enrolled were systematically reviewed. The results revealed that preterm infants had a greater likelihood of childhood obesity (defined as BMI ≥95th percentile for age-sex), than term infants (OR = 1.19, 95% CI [1.13, 1.26]). However, no difference of childhood obesity was found between “small for gestational age”(SGA) and “appropriate for gestational age”(AGA) among preterms. Accelerated weight gain (defined as weight gain velocity during first two years after birth) significantly increased the likelihood of subsequent childhood obesity among preterms (aOR = 1.87, 95% CI [1.57, 2.231]). In conclusion, accelerated weight gain at infancy among preterm children may be a critical contributor to obesity in later life. Establishing optimal growth trajectories and timely referral to health care providers may be of clinical importance.

Association between early weight gain and later adiposity in Sri Lankan adolescents.

Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11-13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0-6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6-18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.

Changes in Daily Step Counts and Health-Related Fitness After a Sports-Based Residential Summer Camp in Boys

Several schoolwide initiatives have been created to combat the rate of obesity in adolescents. However, despite programs showing an ability to advance health-related fitness during the academic year, the summer months contribute to the most accelerated weight gain and health-related fitness (HRF) losses in school aged youth. The purpose of this study was to determine the impact of a residential summer camp on health-related fitness markers in adolescents. The participants were 100 male campers aged 10–14. Campers performed body mass index (BMI) and various physical activity assessments aimed to evaluate health-related fitness levels prior to and following their participation in summer camp. Physical activity levels were assessed throughout the summer using pedometers. MANCOVA results revealed significant pretest to post-test improvements on health-related fitness areas of BMI, aerobic fitness, muscular strength and endurance, and flexibility. The results of this study offer preliminary indications that participation in summer camp programing can promote and maintain health-related fitness levels in adolescents over the summer.

Isocitrate dehydrogenase 2 protects mice from high-fat diet-induced metabolic stress by limiting oxidative damage to the mitochondria from brown adipose tissue

Isocitrate dehydrogenase 2 (IDH2) is an NADP+-dependent enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate in the mitochondrial matrix, and is critical for the production of NADPH to limit the accumulation of mitochondrial reactive oxygen species (ROS). Here, we showed that high-fat diet (HFD) feeding resulted in accelerated weight gain in the IDH2KO mice due to a reduction in whole-body energy expenditure. Moreover, the levels of NADP+, NADPH, NAD+, and NADH were significantly decreased in the brown adipose tissue (BAT) of the HFD-fed IDH2KO animals, accompanied by decreased mitochondrial function and reduced expression of key genes involved in mitochondrial biogenesis, energy expenditure, and ROS resolution. Interestingly, these changes were partially reversed when the antioxidant butylated hydroxyanisole was added to the HFD. These observations reveal a crucial role for IDH2 in limiting ROS-dependent mitochondrial damage when BAT metabolism is normally enhanced to limit weight gain in response to dietary caloric overload.

The Role of Protein and Free Amino Acids on Intake, Metabolism, and Gut Microbiome: A Comparison Between Breast-Fed and Formula-Fed Rhesus Monkey Infants.

Background: Compared to breast-fed (BF), formula-fed (FF) infants exhibit more rapid weight gain, a different fecal microbial profile, as well as elevated serum insulin, insulin growth factor 1 (IGF-1), and branched chain amino acids (BCAAs). Since infant formula contains more protein and lower free amino acids than breast milk, it is thought that protein and/or free amino acids may be key factors that explain phenotypic differences between BF and FF infants.Methods: Newborn rhesus monkeys (Macaca mulatta) were either exclusively BF or fed regular formula or reduced protein formula either supplemented or not with a mixture of amino acids. Longitudinal sampling and clinical evaluation were performed from birth to 16 weeks including anthropometric measurements, intake records, collection of blood for hematology, serum biochemistry, hormones, and metabolic profiling, collection of urine for metabolic profiling, and collection of feces for 16s rRNA fecal microbial community profiling.Results: Reducing protein in infant formula profoundly suppressed intake, lowered weight gain and improved the FF-specific metabolic phenotype in the first month of age. This time-dependent change paralleled an improvement in serum insulin. All lower protein FF groups showed reduced protein catabolism with lower levels of blood urea nitrogen (BUN), urea, ammonia, albumin, creatinine, as well as lower excretion of creatinine in urine compared to infants fed regular formula. Levels of fecal microbes (Bifidobacterium and Ruminococcus from the Ruminococcaceae family), that are known to have varying ability to utilize complex carbohydrates, also increased with protein reduction. Adding free amino acids to infant formula did not alter milk intake or fecal microbial composition, but did significantly increase urinary excretion of amino acids and nitrogen-containing metabolites. However, despite the lower protein intake, these infants still exhibited a distinct FF-specific metabolic phenotype characterized by accelerated weight gain, higher levels of insulin and C-peptide as well as elevated amino acids including BCAA, lysine, methionine, threonine and asparagine.Conclusions: Reducing protein and adding free amino acids to infant formula resulted in growth and metabolic performance of infants that were more similar to BF infants, but was insufficient to reverse the FF-specific accelerated growth and insulin-inducing high BCAA phenotype.

Unintentional error in formula preparation and its simulated impact on infant weight and adiposity.

Accelerated weight gain in infancy is a public health issue and is likely due to feeding behaviours. To test the accuracy of individuals to dispense infant formula as compared with recommended serving sizes and to estimate the effect of dispensing inaccuracy on infant growth. Fifty-three adults dispensed infant formula powder for three servings of 2, 4, 6, and 8 fl oz bottles, in random order. The weight of dispensed infant formula powder was compared with the recommended serving size weight on the nutrition label. A novel mathematical model was used to estimate the impact of formula dispensing on infant weight and adiposity. Nineteen percent of bottles (20 of 636) prepared contained the recommended amount of infant formula powder. Three percent were underdispensed, and 78% of bottles were overdispensed, resulting in 11% additional infant formula powder. Mathematical modelling feeding 11% above energy requirements exclusively for 6 months for male and female infants suggested infants at the 50th percentile for weight at birth would reach the 75th percentile with increased adiposity by 6 months. Inaccurate measurement of infant formula powder and overdispensing, which is highly prevalent, specifically, may contribute to rapid weight gain and increased adiposity in formula-fed infants.

Older Adults with Lowest Risk of Developing Type 2 Diabetes: Results from a Large and Diverse US Cohort (2003–2016) (OR22-06-19)

ObjectivesHigh rates of early obesity substantially increase lifetime risk of developing diabetes. The objective of this research is to examine the impact of this shift on type-2 diabetes risk and aging in a large and diverse U.S. cohort. MethodsA nationally sampled, longitudinal survey, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study (2003–2007), a collection of sociobiological data, were observed through 2013–2016. We included black and white men and women aged ≥45 without diabetes at baseline for whom follow-up data was available. To assess incident diabetes as a function of age, we used the R package Segmented and examined whether this risk was constant over the whole range of age or whether the risk was non-linear with a threshold inflection value. After inspection of the data, age as a continuous variable appeared to have a piecewise relationship with incidence diabetes. A logistic model to see the effect of age on incident diabetes adjusting for sex and race was run. We estimated changes in odds for developing diabetes in ten years by age using restricted cubic spline knots. We estimated the breakpoint statistically using the psi argument in ‘segmented’. Odds ratios for developing diabetes on both sides of the breakpoint were calculated. ResultsBaseline age appeared to show a non-linear association with future diabetes incidence with a breakpoint at age 55 (P = 0.005). After 55 years, incident diabetes declined (slope at age 45–54.9: 0.06; CI: 0.02, 0.10; slope age ≥55: –0.02; CI –0.04, –0.01). Odds ratio for developing diabetes in ten years for those 45–55 years (OR: 1.18, 95% CI 1.02–1.37, P = 0.024) confirm this relationship – those 45–55 years have 18% higher odds of developing diabetes than those over 55. ConclusionsThis model estimated an age breakpoint of roughly 55 years of age when younger individuals were observed to have a progressive increase in incident diabetes while those 55 and older had a declining risk. Between 1992 and 2010, mean BMI in the US increased, resulting primarily from accelerated weight gain among persons initially normal and overweight - our findings argue for a careful data driven approach in considering the effects of age on incident diabetes to derive a more accurate prediction for diabetes. Funding SourcesLua Wilkinson is supported in part by NIH grant T32 DK062710. Supporting Tables, Images and/or Graphs▪

Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance.

Petite Integration Factor 1 (PIF1) is a multifunctional helicase present in nuclei and mitochondria. PIF1 knock out (KO) mice exhibit accelerated weight gain and decreased wheel running on a normal chow diet. In the current study, we investigated whether Pif1 ablation alters whole body metabolism in response to weight gain. PIF1 KO and wild type (WT) C57BL/6J mice were fed a Western diet (WD) rich in fat and carbohydrates before evaluation of their metabolic phenotype. Compared with weight gain-resistant WT female mice, WD-fed PIF1 KO females, but not males, showed accelerated adipose deposition, decreased locomotor activity, and reduced whole-body energy expenditure without increased dietary intake. Surprisingly, PIF1 KO females did not show obesity-induced alterations in fasting blood glucose and glucose clearance. WD-fed PIF1 KO females developed mild hepatic steatosis and associated changes in liver gene expression that were absent in weight-matched, WD-fed female controls, linking hepatic steatosis to Pif1 ablation rather than increased body weight. WD-fed PIF1 KO females also showed decreased expression of inflammation-associated genes in adipose tissue. Collectively, these data separated weight gain from inflammation and impaired glucose homeostasis. They also support a role for Pif1 in weight gain resistance and liver metabolic dysregulation during nutrient stress.

SUN-114 Microglia Interact with Hypothalamic Progenitors during Development and Are Required for Proper Energy Balance

Microglia are the resident mononuclear phagocytic immune cells of the central nervous system (CNS), and are primarily responsible for responding to neural insults and disposing of cellular debris. However, over the last decade studies are showing that microglia are highly dynamic cells involved in various critical neurodevelopmental processes. We set out to study microglia dynamics in the embryonic hypothalamus given that the hypothalamus is responsive to external stressors and critical for maintaining homeostatic processes such as energy balance, thirst, food intake, reproduction, and circadian rhythms. Using slice culture and time-lapse imaging we showed that hypothalamic microglia are highly dynamic during embryogenesis, constantly surveying their environment and often interacting with radial glia precursor cells that line the third ventricle and are responsible for generating hypothalamic neurons, oligodendrocytes, astrocytes, and tanycytes. Moreover, given that microglia colonize the embryonic brain alongside key steps of hypothalamic development, we wanted to test whether microglia are required for the proper establishment of this brain region. To eliminate microglia from the fetal brain, we treated pregnant dams with the Colony-stimulating factor-1 (Csf1r) inhibitor PLX5622, as Csf1r is expressed by microglia and is required for their proliferation, differentiation, and survival. Embryonic microglia depletion resulted in a decreased litter size, as well as an increase in the number of pups that died within the first two postnatal days of life. In pups that survived, the elimination of microglia in the fetal brain resulted in a decrease in the number of Pro-opiomelanocortin (POMC) neurons and a concomitant accelerated weight gain, suggesting that microglia could be important for the development of hypothalamic satiety centers. Depletion of microglia during embryogenesis also had long-term sex-specific effects on behaviour. Furthermore, hypothalamic microglia appear to be sensitive to the endocrine disruptor Bisphenol A during embryogenesis. Taken together, these data demonstrate an important role for microglia during the development of the embryonic hypothalamus.

Potential circadian and circannual rhythm contributions to the obesity epidemic in elementary school age children

Children gain weight at an accelerated rate during summer, contributing to increases in the prevalence of overweight and obesity in elementary-school children (i.e., approximately 5 to 11 years old in the US). Int J Behav Nutr Phys Act 14:100, 2017 explained these changes with the “Structured Days Hypothesis” suggesting that environmental changes in structure between the school year and the summer months result in behavioral changes that ultimately lead to accelerated weight gain. The present article explores an alternative explanation, the circadian clock, including the effects of circannual changes and social demands (i.e., social timing resulting from societal demands such as school or work schedules), and implications for seasonal patterns of weight gain. We provide a model for understanding the role circadian and circannual rhythms may play in the development of child obesity, a framework for examining the intersection of behavioral and biological causes of obesity, and encouragement for future research into bio-behavioral causes of obesity in children.

Early overnutrition reduces Pdx1 expression and induces \u03b2 cell failure in Swiss Webster mice

Childhood obesity and early rapid growth increase the risk for type 2 diabetes. Such early overnutrition can be modeled in mice by reducing litter size. We investigated the effects of early overnutrition and increased dietary fat intake on β cell function in Swiss Webster mice. On a moderate-fat diet, early overnutrition accelerated weight gain and induced hyperinsulinemia in pups. Early overnutrition males exhibited higher β cell mass but reduced islet insulin content and Pdx1 expression. Males had a high diabetes incidence that was increased by early overnutrition, characterized by a progressive increase in insulin secretion as well as β cell death, indicated by histological analysis and increased circulating miR-375 levels. Females maintained normoglycemia throughout life. High-fat diet (HFD) increased diabetes incidence in males, whereas low-fat diet was completely protective. This protective effect was abolished in early overnutrition males transiently exposed to HFD in early life. Although Swiss Webster mice are not known to be diabetes-prone, the high diabetes incidence suggests an underlying genetic susceptibility that can be induced by overnutrition and increased dietary fat intake in early life. Thus, the nutritional environment in early life may impact long-term β cell function and increase diabetes risk, particularly in genetically susceptible individuals.

Accelerated Weight Gain Subsequent to Postnatal Slow Weight Gain and Overweight Risk in Early Childhood: A Nested Case-Control Study

Background: The effects of accelerated weight gain (AWG) immediately after a postnatal slow weight gain (PSWG) on the risk of later overweight is unknown. The objective of this study was to assess the relationship between AWG after PSWG and overweight risk at 3 years of age. Methods: This nested case-control study included 255 subjects born at term, appropriate for gestational age, and with normal birth weight but PSWG (< 0.67 SD score) until 3–4 months of age. Overweight cases at 3 years of age were defined according to International Obesity Task Force criteria. The association between AWG after PSWG and overweight status at age 3 years was analyzed by the Fisher’s exact, Breslow-Day, and Mantel-Haenszel tests. Results: Seven of the subjects that showed AWG after PSWG were deemed overweight at age 3. An AWG from 6–9 to 17–20 months after PSWG during the first 3–4 months of life had the most significant association with overweight status at 3 years of age (adjusted OR 10.06, 95% CI 1.74–58.01, p value: 0.0022). Conclusions: AWG immediately after PSWG, even occurring at only 1 of 3 interval from 3–4 to 6–9 months, from 6–9 to 17–20 months, and 17–20 months to 3 years after PSWG, leads to an overweight status at 3 years of age. Monitoring weight growth after PSWG may help identify AWG and later overweight risk.

Sustained obesity starts in early childhood

Accelerated weight gain during early childhood predicts sustained obesity.

Body mass index, peer victimization, and body dissatisfaction across 7years of childhood and adolescence: Evidence of moderated and mediated pathways.

Numerous studies have reported that children and adolescents who are overweight are more likely to get bullied, yet the literature is replete with methodological limitations. We examined the transactional associations between peer victimization and body mass index (BMI), considering potential mediating (body dissatisfaction) and moderating (biological sex) factors. Participants (n=631) came from the McMaster Teen Study, where students were assessed annually between Grades 5-11, approximately half were girls (53.9%), and the majority were white (76.4%). Peer victimization (from Grade 5) and body dissatisfaction (from Grade 6) were self-reported by students, while parents reported their child's height and weight (from Grade 5). Cascade models were built up sequentially using path analysis across 2-year increments (Grades 5, 7, 9, and 11). The final model had excellent fit to the data (χ2 =73.961, df=66, p=0.234). Grade 5 peer victimization had a direct effect on BMI across a 2-year period in girls (b=0.59, SE=0.21, p=0.005) and boys (b=0.82, SE=0.30, p=0.006), and an indirect effect on BMI via body dissatisfaction across a 4-year period (b=0.074, 95% CI=0.012-0.152, p=0.036). At no point did BMI directly increase risk for peer victimization, yet there were indirect effects via body dissatisfaction among girls but not boys. Peer victimization and body dissatisfaction were proximally and longitudinally related at every time point and there was a transactional association in late-adolescence among girls but not boys. Targeting modifiable factors in the social (peer victimization) and psychological (body dissatisfaction) domains may limit accelerated weight gain and the health risks associated with excess adiposity.

Loss of HDAC6 alters gut microbiota and worsens obesity.

Alterations in gut microbiota are known to affect intestinal inflammation and obesity. Antibiotic treatment can affect weight gain by elimination of histone deacetylase (HDAC) inhibitor-producing microbes, which are anti-inflammatory by augmenting regulatory T (Treg) cells. We asked whether mice that lack HDAC6 and have potent suppressive Treg cells are protected from microbiota-induced accelerated weight gain. We crossed wild-type and HDAC6-deficient mice and subjected the offspring to perinatal penicillin, inducing weight gain via microbiota disturbance. We observed that male HDAC6-deficient mice were not protected and developed profoundly accelerated weight gain. The antibiotic-exposed HDAC6-deficient mice showed a mixed immune phenotype with increased CD4+ and CD8+ T-cell activation yet maintained the enhanced Treg cell-suppressive function phenotype characteristic of HDAC6-deficient mice. 16S rRNA sequencing of mouse fecal samples reveals that their microbiota diverged with time, with HDAC6 deletion altering microbiome composition. On a high-fat diet, HDAC6-deficient mice were depleted in representatives of the S24-7 family and Lactobacillus but enriched with Bacteroides and Parabacteroides; these changes are associated with obesity. Our findings further our understanding of the influence of HDACs on microbiome composition and are important for the development of HDAC6 inhibitors in the treatment of human diseases.-Lieber, A. D., Beier, U. H., Xiao, H., Wilkins, B. J., Jiao, J., Li, X. S., Schugar, R. C., Strauch, C. M., Wang, Z., Brown, J. M., Hazen, S. L., Bokulich, N. A., Ruggles, K. V., Akimova, T., Hancock, W. W., Blaser, M. J. Loss of HDAC6 alters gut microbiota and worsens obesity.

Depletion of embryonic microglia using the CSF1R inhibitor PLX5622 has adverse sex-specific effects on mice, including accelerated weight gain, hyperactivity and anxiolytic-like behaviour

Microglia are the resident immune cells in the central nervous system (CNS). Originally thought to be primarily responsible for disposing of cellular debris and responding to neural insults, emerging research now shows that microglia are highly dynamic cells involved in a variety of neurodevelopmental processes. The hypothalamus is a brain region critical for maintaining homeostatic processes such as energy balance, thirst, food intake, reproduction, and circadian rhythms. Given that microglia colonize the embryonic brain alongside key steps of hypothalamic development, here we tested whether microglia are required for the proper establishment of this brain region. The Colony-stimulating factor-1 receptor (Csf1r) is expressed by microglia, macrophages and osteoclasts, and is required for their proliferation, differentiation, and survival. Therefore, to eliminate microglia from the fetal brain, we treated pregnant dams with the CSF1R inhibitor PLX5622. We showed that approximately 99% of microglia were eliminated by embryonic day 15.5 (E15.5) after pregnant dams were placed on a PLX5622 diet starting at E3.5. Following microglia depletion, we observed elevated numbers of apoptotic cells accumulating throughout the developing hypothalamus. Once the PLX5622 diet was removed, microglia repopulated the postnatal brain within 7 days and did not appear to repopulate from Nestin+ precursors. Embryonic microglia depletion also resulted in a decreased litter size, as well as an increase in the number of pups that died within the first two postnatal days of life. In pups that survived, the elimination of microglia in the fetal brain resulted in a decrease in the number of Pro-opiomelanocortin (POMC) neurons and a concomitant accelerated weight gain starting at postnatal day 5 (P5), suggesting that microglia could be important for the development of cell types key to hypothalamic satiety centers. Moreover, surviving PLX5622 exposed animals displayed craniofacial and dental abnormalities, perhaps due to non-CNS effects of PLX5622 on macrophages and/or osteoclasts. Finally, depletion of microglia during embryogenesis had long-term sex-specific effects on behaviour, including the development of hyperactivity and anxiolytic-like behaviour in juvenile and adult female mice, respectively. Together, these data demonstrate an important role for microglia during the development of the embryonic hypothalamus, and perhaps the CNS more broadly.

More rapid increase in BMI from age 5–15 is associated with elevated weight status at age 24 among non-Hispanic white females

BackgroundA rapidly increasing BMI trajectory throughout childhood is associated with negative health outcomes in adulthood such as obesity, cardiovascular disease, and diabetes. The purpose of the current study was to assess whether BMI trajectories from age 5–15 predicted changes in weight and BMI from adolescence to adulthood, and dieting-related behaviors in young adulthood. MethodsNon-Hispanic White female participants from Early Dieting in Girls (n = 182), a longitudinal cohort study, were followed from age 5 to 15 and completed a follow-up survey at age 24. Participants were classified by age 5–15 BMI trajectory groups: UPC, accelerated weight gain from age 5–9; DDPC, accelerated weight gain from 5 to 9 followed by a decrease; 60PT, weight tracked along 60th percentile; 50PT, weight tracked along 50th percentile. Data at age 24 included self-reported weight, height, dietary restraint, disinhibition, and dieting. ResultsMajority of participants (80.8%) completed the follow-up survey; of these participants, 60% in UPC group had obesity at age 24, compared to <10% in the other 3 groups. Participants in the UPC group had greater increases in BMI since age 15, compared to the 50PT group, and trend-level greater weight increases than those in the DDPC and 60PT groups. Dietary restraint, but not disinhibition, differed across the groups. ConclusionsChildren with accelerated weight gain continued to have the greatest weight gain from adolescence to adulthood and the highest prevalence of obesity in adulthood.

Are birthweight and postnatal weight gain in childhood associated with blood pressure in early adolescence? Results from a Ugandan birth cohort.

BackgroundIn Africa, where low birthweight (LBW), malnutrition and high blood pressure (BP) are prevalent, the relationships between birthweight (BW), weight gain and BP later in life remain uncertain. We examined the effects of early life growth on BP among Ugandan adolescents.MethodsData were collected prenatally from women and their offspring were followed from birth, with BP measured following standard protocols in early adolescence. Weight-for-age Z-scores (WAZ) were computed using World Health Organization references. Linear regression was used to relate BW, and changes in WAZ between birth and 5 years, to adolescents’ BP, adjusting for confounders.ResultsAmong 2345 live offspring, BP was measured in 1119 (47.7%) adolescents, with mean systolic BP 105.9 mmHg and mean diastolic BP 65.2 mmHg. There was little evidence of association between BW and systolic [regression coefficient β = 0.14, 95% confidence interval (CI) (-1.00, 1.27)] or diastolic [β = 0.43, 95% CI (-0.57, 1.43)] BP. Accelerated weight gain between birth and 5 years was associated with increased BP: systolic β = 1.17, 95% CI (0.69, 1.66) and diastolic β = 1.03, 95% CI (0.59, 1.47). Between birth and 6 months of age, effects of accelerated weight gain on adolescent BP were strongest among the LBW (both premature and small-for-gestational-age) children [BW < 2.5 kg: β = 2.64, 95% CI (0.91, 4.37), BW≥2.5 kg: β = 0.58, 95% CI (0.01, 1.14), interaction P-value = 0.024].ConclusionsFindings from this large tropical birth cohort in Uganda suggest that postnatal weight gain rather than BW is important in the developmental programming of BP, with fast-growing LBW children at particular risk. Efforts to control BP should adopt a life course approach.