Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19–24 kg/m2; n = 12) and obese groups (BMI, 32–43 kg/m2; n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by ≥1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-κB(p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1α protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress.

Our results indicated that obese but otherwise healthy children have different regional gray and white matter development in the brain and differences in white matter microstructures compared with healthy normal weight children.

Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as single-stranded or double-stranded RNA or DNA viruses. At concentrations ranging from physiological to supraphysiological (3.7-370 muM), flavonoids, including genistein, have been shown to reduce the infectivity of a variety of viruses affecting humans and animals, including adenovirus, herpes simplex virus, human immunodeficiency virus, porcine reproductive and respiratory syndrome virus, and rotavirus. Although the biological properties of the flavonoids are well studied, the mechanisms of action underlying their antiviral properties have not been fully elucidated. Current results suggest a combination of effects on both the virus and the host cell. Isoflavones have been reported to affect virus binding, entry, replication, viral protein translation and formation of certain virus envelope glycoprotein complexes. Isoflavones also affect a variety of host cell signaling processes, including induction of gene transcription factors and secretion of cytokines. The efficacy of isoflavones and related flavonoids in virus infectivity in in vitro bioassays is dependent on the dose, frequency of administration and combination of isoflavones used. Despite promising in vitro results, there is lack of data confirming the in vivo efficacy of soy isoflavones. Thus, investigations using appropriate in vivo virus infectivity models to examine pharmacological and especially physiological doses of flavonoids are warranted.

Objective: The longitudinal trajectories of body composition of children born to mothers with normal weight, overweight, and obesity have not been evaluated using precise body composition methods. This study investigated the relationship between maternal prepregnancy BMI and offspring body composition trajectories during the first 6 years of life. Methods: Healthy infants (N 5 325) were assessed longitudinally (at ages 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, and 6 years) using dual-energy X-ray absorptiometry. Mixed-effects regression for repeated measures was used to model each continuous outcome as a function of maternal BMI and covariates (race, gestational age, birth weight, and mode of infant feeding).Results: Maternal obesity differentially impacted body fat, but not bone mineral content or density, of girls and boys. Boys born to mothers with obesity have higher body fat from ages 2-6 years compared to boys born to normal-weight and overweight mothers (P < 0.05), whereas body composition of girls born to mothers with obesity was not different across groups during the first 6 years of life (P > 0.05).Conclusions: This clinical observational study demonstrates a sexual dimorphism in offspring body composition until age 6 years based on maternal BMI, with a greater effect of maternal adiposity seen in boys than in girls.

Human milk oligosaccharides (HMOs) are bioactive molecules playing a critical role in infant health. We aimed to quantify the composition of HMOs of women with normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obesity (30.0–60.0 kg/m2) and determine the effect of HMO intake on infant growth. Human milk (HM) samples collected at 2 months (2 M; n = 194) postpartum were analyzed for HMO concentrations via high-performance liquid chromatography. Infant HM intake, anthropometrics and body composition were assessed at 2 M and 6 M postpartum. Linear regressions and linear mixed-effects models were conducted examining the relationships between maternal BMI and HMO composition and HMO intake and infant growth over the first 6 M, respectively. Maternal obesity was associated with lower concentrations of several fucosylated and sialylated HMOs and infants born to women with obesity had lower intakes of these HMOs. Maternal BMI was positively associated with lacto-N-neotetraose, 3-fucosyllactose, 3-sialyllactose and 6-sialyllactose and negatively associated with disialyllacto-N-tetraose, disialyllacto-N-hexaose, fucodisialyllacto-N-hexaose and total acidic HMOs concentrations at 2 M. Infant intakes of 3-fucosyllactose, 3-sialyllactose, 6-sialyllactose, disialyllacto-N-tetraose, disialyllacto-N-hexaose, and total acidic HMOs were positively associated with infant growth over the first 6 M of life. Maternal obesity is associated with changes in HMO concentrations that are associated with infant adiposity.

The contributions of maternal diet and obesity in shaping offspring microbiome remain unclear. Here we employed a mouse model of maternal diet-induced obesity via high-fat diet feeding (HFD, 45% fat calories) for 12 wk prior to conception on offspring gut microbial ecology. Male and female offspring were provided access to control or HFD from weaning until 17 wk of age. Maternal HFD-associated programming was sexually dimorphic, with male offspring from HFD dams showing hyper-responsive weight gain to postnatal HFD. Likewise, microbiome analysis of offspring cecal contents showed differences in α-diversity, β-diversity and higher Firmicutes in male compared to female mice. Weight gain in offspring was significantly associated with abundance of Lachnospiraceae and Clostridiaceae families and Adlercreutzia, Coprococcus and Lactococcus genera. Sex differences in metagenomic pathways relating to lipid metabolism, bile acid biosynthesis and immune response were also observed. HFD-fed male offspring from HFD dams also showed worse hepatic pathology, increased pro-inflammatory cytokines, altered expression of bile acid regulators (Cyp7a1, Cyp8b1 and Cyp39a1) and serum bile acid concentrations. These findings suggest that maternal HFD alters gut microbiota composition and weight gain of offspring in a sexually dimorphic manner, coincident with fatty liver and a pro-inflammatory state in male offspring.

Background Studies indicate that maternal weight status modulates human milk composition; however, results are conflicting. Objectives Our objective was to examine the relation between maternal body composition and human milk macronutrients and bioactive components and also their association with infant daily intakes and body composition. Methods Human milk samples were obtained from a longitudinal study (NCT 01131117) in normal weight (NW: 18.5–24.9 kg/m2, n = 88) and overweight/obese (OW: 25–35 kg/m2, n = 86) women between 0.5 and 9 mo postpartum. Macronutrient content was estimated using mid-infrared spectroscopy. Leptin, insulin, and C-reactive protein (CRP) were measured using electrochemiluminescence immunoassays. Infant body composition was obtained using quantitative MRI. Linear mixed models were adjusted for postpartum age and infant sex. Results Human milk in OW mothers was higher in fat and protein and lower in carbohydrate content at some time points compared with that in NW mothers. Human milk leptin, insulin, and CRP concentrations were higher in OW mothers compared with NW mothers, with infants of OW mothers exposed to 1.5–2.5 times higher concentrations of leptin and insulin compared with infants of NW mothers. Similar results were observed when concentrations were normalized to infant daily intake and body weight. The effect sizes of infant daily intakes associated with infant growth parameters were small for macronutrients [0.005–0.05 z-score units and 0.02–0.45 fat mass index (FMI) or fat-free mass index units per unit of change in composition, P &lt; 0.05]. Larger effect sizes were seen with human milk insulin and leptin (0.24 z-score units and 0.37–1.15 FMI units per unit of change in composition, P &lt; 0.05). Conclusions These findings demonstrate that infants of OW mothers are exposed to higher concentrations of insulin, leptin, and, to a lesser extent, CRP. The bioavailability of these 3 human milk bioactives and their mechanisms of action in the infant are unclear. This trial was registered at clinicaltrials.gov as NCT01131117.

BACKGROUND AND OBJECTIVE: Although soy formula has been reported to support normal development, concerns exist regarding potential adverse developmental effects of phytochemicals associated with soy protein. This study characterized developmental status (mental, motor, and language) of breastfed (BF), milk-based formula–fed (MF), or soy protein–based formula–fed (SF) infants during the first year of life. METHODS: Healthy infants (N = 391) were assessed longitudinally at ages 3, 6, 9, and 12 months. Development was evaluated by using the Bayley Scales of Infant Development and the Preschool Language Scale-3. Mixed effects models were used while adjusting for socioeconomic status, mother’s age and IQ, gestational age, gender, birth weight, head circumference, race, age, and diet history. RESULTS: No differences were found between formula-fed infants (MF versus SF). BF infants scored slightly higher than formula-fed infants on the Mental Developmental Index (MDI) score at ages 6 and 12 months (P &lt; .05). Infants who were breastfed also had higher Psychomotor Development Index scores than SF infants at age 6 months and slightly higher Preschool Language Scale-3 scores than MF infants at ages 3 and 6 months (P &lt; .05). In addition, BF infants had a lower probability to score within the lower MDI quartile compared with MF infants and a higher likelihood to score within the upper quartile for the MDI and Psychomotor Development Index compared with SF infants. CONCLUSIONS: This unique study showed that all scores on developmental testing were within established normal ranges and that MF and SF groups did not differ significantly. Furthermore, this study demonstrated a slight advantage of BF infants on cognitive development compared with formula-fed infants.