Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

Context: Infants born small for gestational age (SGA) have increased risk for obesity and metabolic syndrome, but the underlying mechanisms are not fully elucidated. Adipocyte fatty acid–binding protein (AFABP) is an adipokine that has been implicated in modulation of insulin sensitivity and lipid metabolism. Higher plasma AFABP levels are associated with increased risk of metabolic syndrome and cardiovascular morbidity in adults. Alterations in AFABP levels during fetal growth have not been characterized. Objective: To examine AFABP levels in neonatal cord blood in relation to gestational age and birth weight. Design: A cross-sectional study of 361 neonates born at a tertiary academic center. Outcome Measures: Plasma AFABP levels were measured by enzyme-linked immunosorbent assay. For comparison, venous samples from 26 adults were analyzed. Results: AFABP levels were higher in neonates compared with adults (P < 0.01). Preterm infants had higher AFABP levels [48.2 (31.2 to 73.3) ng/mL] compared with full-term infants [35.8 (25.1 to 51.5)] ng/mL, P < 0.01). There was a negative correlation between AFABP and gestational age (r = 0.28, P = 0.02). Among full-term infants, AFABP levels in SGA infants were lower [28.6 (24.2 to 37.3) ng/mL], compared with appropriate for gestational age [36.1 (25.5 to 50.4) ng/mL] and large for gestational age infants [45.0 (24.6 to 62.4) ng/mL, P < 0.05]. Conclusions: These associations may reflect the higher metabolic activity during fetal development. AFABP may also be involved in fetal growth and the association between SGA status and obesity and metabolic syndrome in later life.

Context: Autism spectrum disorders (ASDs) are a group of conditions characterized by impaired social function and repetitive behaviors. Their etiology is largely unknown. Objective: This work aims to examine the associations of maternal second-trimester and cord blood leptin and adiponectin levels with ASDs in offspring. Methods: We used data from 1164 mother-child pairs enrolled in Project Viva, a prospective prebirth cohort. We used logistic regression analysis to examine the associations of leptin and adiponectin levels in maternal second-trimester blood and cord blood obtained at birth with ASDs. Additionally, we examined the association of maternal prepregnancy body mass index (BMI) as an exposure. Main outcome measures included doctor-diagnosed ASDs reported by mothers using questionnaires in midchildhood and early adolescence. Results: The cumulative incidence of ASDs was 3.4%. Maternal prepregnancy BMI (per 5 points) was positively associated with ASDs in a logistic regression model adjusted for maternal race/ethnicity, education, smoking status and child sex (adjusted odds ratio [OR] 1.38; 95% CI, 1.06-1.79). Higher second-trimester adiponectin was associated with lower odds of ASD in offspring (unadjusted OR 0.49; 95% CI, 0.30-0.78; and OR 0.54; 95% CI, 0.32-0.91 after adjusting for maternal race/ethnicity, education, child sex, OR 0.55; 95% CI, 0.33-0.93 after adjusting for BMI, gestational weight gain, gestational diabetes, and smoking status). Maternal leptin and cord blood leptin and adiponectin levels were not associated with ASDs. Conclusion: Prepregnancy BMI and adiponectin during pregnancy may be useful as a tool to monitor the risk of autism. Increasing adiponectin levels prenatally may play a role in the prevention of ASDs.

Context: Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood. Objective: To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants. Design/Methods: In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations. Main Outcome Measures: Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks’ postmenstrual age (PMA). Results: Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks’ PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (−0.36 [−0.64, −0.07]). Insulin was not associated with growth outcomes. Conclusions: Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.

The role of fetal and neonatal growth in the development of adult-onset diseases such as obesity and metabolic syndrome has become increasingly appreciated. Fibroblast growth factor-21 (FGF-21) is known as a regulator of glucose and lipid metabolism. FGF-21 levels are elevated in obese adults and children. The role of FGF-21 in neonatal growth in preterm infants is not known. We aimed to evaluate the association of circulating FGF-21 levels in the first week of life and neonatal growth parameters at the time of discharge from NICU. We performed a longitudinal study of 25 preterm neonates admitted to NICU. Blood samples were collected at two time points: within 24 h of life (T1), and 24–96 h after the first blood draw (T2). FGF-21 levels were measured in plasma by ELISA. Weight, length, BMI and their Z-scores were measured at the time of birth and discharge. The FGF-21 levels were significantly higher at T2 than at T1 (p < 0.001). FGF-21 levels at both time points were positively correlated with gestational age (r = 0.43, p = 0.03). FGF-21 at T1 was positively associated with weight Z-score (β = 0.19, p = 0.001) and length Z-score at discharge (β = 0.21, p = 0.03). Circulating FGF-21 levels increase significantly in the first week, and the FGF-21 levels within the first 24 h are positively associated with weight and length Z-scores at discharge in preterm infants. These results suggest that FGF-21 may be involved in growth and developmental maturation.