Search

Key points The prevalence of obesity and non-alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible etiology as it is thought to be more lipogenic than glucose. In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance. Multiple metabolites including lipids, bile acids, carbohydrates, and amino acids were altered in liver in a sex-specific manner at 6 weeks of age. Some of these changes were also present in adulthood even though HFCS exposure ended at 6 weeks. HFCS significantly altered the gut microbiome which was associated with changes in key microbial metabolites. These results suggest that HFCS intake during adolescence has profound metabolic changes that are linked to changes in the microbiome and these changes are sex-specific. Abstract The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20 years has been linked to increased high fructose corn syrup (HFCS) consumption making it essential to determine the short and long-term effects of HFCS during this vulnerable developmental window. We hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signaling pathways and alters gut microbial composition contributing to changes in energy metabolism with sex-specific effects. C57bl/6J mice with free access to HFCS during adolescence (3-6 weeks of age) underwent glucose tolerance and body composition testing and hepatic metabolomics, gene expression and triglyceride content analysis at 6 and 30 weeks of age (n = 6-8 per sex). At 6 weeks HFCS-exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides (females) and de novo lipogenesis gene expression (ACC, DGAT, FAS, ChREBP, SCD, SREBP, CPT and PPARα) with sex-specific effects. At 30 weeks HFCS-exposed mice also had abnormalities in glucose tolerance (males) and fat mass (females). HFCS exposure enriched carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6 weeks with changes in secondary bile metabolism at 6 and 30 weeks. Microbiome studies performed immediately before and after HFCS exposure identified profound shifts of microbial species in male mice only. In summary, a short-term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which continue to be altered in adulthood, and changes the microbiome in a sex-specific manner. This article is protected by copyright. All rights reserved.

To investigate effects of betamethasone on fetal growth and neonatal outcomes in twins.A retrospective cohort study was conducted of twins delivered at one center in Berlin, Germany, between 1993 and 2011. The betamethasone group included twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to betamethasone between 23(+5) and 33(+6) weeks. The control group included twin pregnancies with no betamethasone exposure matched for length at delivery. Fetal growth and neonatal anthropometric data were analyzed by twin-pair structure, dose, and gestational age (linear mixed model).Overall, 1922 live-born twin pairs (653 betamethasone group, 1269 controls) were included. Compared with controls, late-preterm twins exposed to betamethasone were lighter (mean difference -126g), had a smaller head circumference (-0.4cm), and a shorter body length (-0.8cm) after adjustment for confounders (P0.05). Female neonates from mixed or same-sex twin pairs had a lower birth weight than controls (betamethasone ≤16mg: -114g; betamethasone 24mg: -124g; betamethasone24mg: -187g), with no detectable improvement in neonatal morbidity (hyperbilirubinemia, respiratory distress, asphyxia) or mortality.Betamethasone reduced birth weight, head circumference, and length of female preterm neonates in twin pairs in a dose-dependent manner. The neonatal mortality and morbidity were not improved by betamethasone.

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) share risk associations of adiposity and insulin resistance. We examined the impact of a PCOS diagnosis on the metabolic phenotype of adolescent girls with NAFLD and compared this to girls without PCOS or NAFLD and to age-matched boys. Methods: Community-based adolescents from the Raine Cohort participated in assessments for NAFLD (572 girls and 592 boys) and PCOS (244 girls). One hundred and ninety-nine girls attended both assessments. Results: Amongst the 199 girls, PCOS was diagnosed in 16.1% and NAFLD in 18.6%. NAFLD was diagnosed in 10.1% of the boys. NAFLD was more prevalent in girls with PCOS than girls without PCOS (37.5% vs 15.1%, P = 0.003). Girls with NAFLD plus PCOS had greater adiposity (waist circumference, body mass index, suprailiac skinfold thickness [SST], serum androgens, high-sensitivity C-reactive protein, ferritin, homeostasis model assessment for insulin resistance (HOMA-IR), and lower serum sex hormone binding globulin levels than girls with NAFLD without a PCOS diagnosis (all P

Fructose is an increasingly common constituent of the Westernized diet due to cost and production efficiencies. Although an integral component of our pre-industrial revolution diet, over the past two decades human and animal studies have highlighted that excessive fructose intake appears to be associated with adverse metabolic effects. Excessive intake of fructose is the combined result of increased total energy consumption and increased portion sizes of foods, which often incorporate the fructose-containing sugars sucrose and high-fructose corn-syrup (HFCS). The adverse metabolic effects following excessive fructose consumption have become a hot topic in mainstream media and there is now rigorous scientific debate regarding periods of exposure, dosage levels, interactive effects with other sugars and fats and mechanisms underlying the actions of fructose. There is still a degree of controversy regarding the extent to which sugars such as sucrose and HFCS have contributed to the current epidemic of obesity and diabetes. Furthermore, an increasing number of infants are being exposed to sugar-sweetened food and beverages before birth and during early postnatal life, highlighting the importance of determining the long-term effects of this perinatal exposure on the developing offspring. There are limited human observational and controlled studies identifying associations of excessive sweetened food and beverage consumption with poor pregnancy outcomes. Animal research has demonstrated an increased incidence of gestational diabetes as well as altered maternal, fetal and offspring metabolic function, although the long-term effects and the mechanism underlying these perturbations are ill defined. This review aims to understand the role of early life fructose exposure in modifying postnatal risk of disease in the offspring, focusing on fructose intake during pregnancy and in early postnatal life.

We have previously reported that offspring of mothers fed a high fat (HF) diet during pregnancy and lactation enter puberty early and are hyperleptinaemic, hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also impact offspring development and disease risk.We therefore hypothesized that prenatal nutrition would affect maternal care and that an interaction may exist between a maternal HF diet and maternal care, subsequently impacting on offspring phenotype.Wistar rats were mated and randomized to control dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Maternal care was assessed by observing maternal licking and grooming of pups between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a control (–con) or HF (–hf) diet. From P27, pubertal onset was assessed. At ∼P105 oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF-fed mothers licked and groomed pups less than CON dams.Maternal fat:lean ratio was higher in HF dams at weaning and was associated with higher maternal plasma leptin and insulin concentrations, but there was no effect of maternal care on fat:lean ratio or maternal hormone levels. Both female and male offspring of HF dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF offspring were heavier than controls. Prepubertal retroperitoneal fat mass was greater in pups from HF-fed dams compared to CON and was associated with elevated circulating leptin concentrations in females only, but there was neither an effect of maternal care, nor an interaction between maternal diet and care on prepubertal fat mass. Pups from HF-fed dams went into puberty early and this effect was exacerbated by a postweaning HF diet.Maternal and postweaning HF diets independently altered oestrous cyclicity in females: female offspring of HF-fed mothers were more likely to have prolonged or persistent oestrus, whilst female offspring fed a HF diet postweaning were more likely to have irregular oestrous cycles and were more likely to have prolonged or persistent oestrus. These data indicate that maternal HF nutrition during pregnancy and lactation results in a maternal obese phenotype and has significant impact on maternal care during lactation. Maternal and postweaning nutritional signals, independent of maternal care, alter offspring body fat pre-puberty and female reproductive function in adulthood, which may be associated with advanced ovarian ageing and altered fertility.

Aim Fetal androgens influence fetal growth as well as postnatal neurocognitive ability. However, to our knowledge, no published study has prospectively examined the impact of early-life androgens on infant brain growth. We report the association between circulating fetal androgen levels, measured from umbilical-cord blood at birth, and a proxy measure of brain growth: head circumference. Method Participants were 82 unselected female infants from a large representative birth cohort (mean gestational age 39.4wks, SD 1.7). Umbilical-cord blood was obtained at birth and analysed for androgen concentrations (total testosterone, androstenedione, dehyrdroepiandrosterone, and its sulphated metabolite). Head circumference and two other measures of growth – weight (mean 3311.4g, SD 461.3) and length – were measured within 3 days of birth and again at approximately 1 year of age (mean age 13.1mo, SD 1.1). Results Multivariate linear regressions found an inverse association between levels of free testosterone and growth in head circumference (correlation=−.24), even when adjusting for sociodemographic/obstetric covariates and head size at birth. Growth in weight and length could not be predicted by free testosterone concentration. Interpretation This is the first report of an association between prenatal androgen levels and postnatal growth in head circumference. These findings suggest that early-life androgens may impact brain development during infancy.

OBJECTIVE: To determine the role of carotid sinus innervation on differential fetal organ growth during maternal nutrient restriction in late pregnancy. DESIGN: Randomised controlled study. SETTING: University research facility. SAMPLE: Thirty-nine Merino ewes. METHODS: At 113 days gestational age (dGA), fetuses were bilaterally carotid sinus denervated or sham denervated. From 118 dGA, the surgery groups were subdivided into two dietary groups, and their ewes were fed 100% of nutrient requirements or 50% until tissue collection at 140 dGA. This provided four groups (sham/control diet, sham/restricted diet, denervated/control diet and denervated/restricted diet). MAIN OUTCOME MEASURES: Fetal organ weights and hormone levels and maternal weight change during the dietary restriction. RESULTS: Adrenal glands were larger in sham/restricted diet fetuses than in sham/control diet or denervated/restricted diet fetuses (P < 0.05). Fetal adrenal weight and brain-to-liver weight ratio were positively related to maternal weight change during the nutritional challenge in sham fetuses only (P < 0.05). Fetal liver weight was negatively related to maternal weight change during nutritional challenge in sham fetuses only (P < 0.05). CONCLUSIONS: We have shown a reduction in liver growth but sparing of adrenal growth in response to moderate maternal undernutrition, which is dependent on intact carotid body innervation. This suggests a new role for the carotid bodies in the control of differential organ growth during such undernutrition