The effects of maternal obesity on lung development have been recognized, and speculation is that these diseases are not simply because of accelerated pulmonary decline with aging but with a failure to achieve optimal lung development during early life. These studies tested the hypothesis that maternal obesity alters signaling pathways during the course of lung development that may affect life-long pulmonary health. Adult female mice were fed 60% fat [high-fat diet (HFD)] or 10% fat [control diet (CD)] for 8 wk before mating and through weaning. Pup lung tissues were collected at postnatal days ( PN) 7, 21, and 90 (after receiving HFD or CD as adults). At PN7, body weights from HFD were greater than CD but lung weight-to-body weight ratios were lower. In lung tissues, NFκB-mediated inflammation was greater in HFD pups at PN21 and phospho-/total STAT3, phospho-/total VEGF receptor 2, and total AKT protein levels were lower with maternal HFD and protein tyrosine phosphatase B1 levels were increased. Decreased platelet endothelial cell adhesion molecule levels were observed at PN21 and at PN90 in the pups exposed to maternal HFD. Morphometry indicated that the pups exposed to maternal or adult HFD had fewer alveoli, and the effect was additive. Decreases in pulmonary resistance, elastance, and compliance were observed because of adult HFD diet and decreases in airway resistance and increases in inspiratory capacity because of maternal HFD. In conclusion, maternal HFD disrupts signaling pathways in the early developing lung and may contribute to deficiencies in lung function and increased susceptibility in adults.

BACKGROUND: Intrauterine infection and/or inflammation (Triple I) is an important cause of preterm birth (PTB) and adverse newborn outcomes. N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug safely administered to pregnant women with acetaminophen toxicity. METHODS: We conducted a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I. Participants (n = 67) were randomized to an intravenous infusion of NAC or placebo mimicking the FDAapproved regimen. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Newborns exposed to NAC (n = 33) had significantly improved status at birth and required less intensive resuscitation compared to placebo (n = 34). Fewer NAC-exposed newborns developed two or more prematurity-related severe morbidities [NAC: 21% vs. placebo: 47%, relative risk, 0.45; 95% confidence interval (CI) 0.21-0.95] with the strongest protection afforded against bronchopulmonary dysplasia (BPD, NAC: 3% vs. placebo: 32%, relative risk, 0.10; 95% CI: 0.01-0.73). These effects were independent of gestational age, birth weight, sex, or race. Umbilical cord plasma NAC concentration correlated directly with cysteine, but not with plasma or whole blood glutathione. NAC reduced the placental expression of histone deacetylase-2, suggesting that epigenetic mechanisms may be involved. CONCLUSIONS: These data provide support for larger studies of intrapartum NAC to reduce prematurity-related morbidity.

BackgroundElectronic cigarette usage is increasing at an alarming rate primarily because of reports implicating their use as safer than traditional cigarettes. However, little is known about the acute effects on lung injury and inflammation. These studies tested the hypothesis that acute exposure to e‐cigarette vapor would result in lung inflammation and injury.MethodsC57Bl/6 mice were exposed to e‐cigarette vapor consisting of 10 mg/mL nicotine in a 50/50 mixture of propylene glycol/vegetable glycerin (PG/VG) or PG/VG alone for 6 hr/day, 5 days/week for either 1 or 2 weeks. Lungs were excised and snap‐frozen for analysis. Lung homogenates were analyzed by western blot for pAKT, pSTAT3, PECAM, BCL‐2, and BAX. RNA was isolated for measurement of MMP9, KC, and VEGF by RT‐PCR.ResultspAKT protein expression was decreased (0.54 vs 1.0 relative density, p=0.02) and pSTAT3 was increased (1.7 vs 1.0 relative density, p=0.02) in the e‐cigarette exposed mice vs PG/VG exposed mice after 1 week of exposure. At 2 weeks, pSTAT3 remained increased (1.9 vs 1.0 relative density, p=0.01) and both BCL‐2 (2.5 vs 1.0 relative density, p=0.02) and BAX (1.7 vs 1.0 relative density, p<0.05) were increased in the exposed mice compared to mice exposed to PG/VG alone. No differences were observed in PECAM, MMP9, KC, or VEGF.ConclusionsAcute exposure to e‐cigarette vapor caused changes in signaling molecules associated with apoptosis. While we did not observe differences in the inflammatory pathways tested, additional inflammatory and apoptotic markers may yield insights into the acute effects of e‐cigarette vapor exposure on the lung.Support or Funding InformationNIH NHLBI R01 HL139348 02This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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BackgroundMaternal obesity has been associated with multiple complications for both the mother and the child including hypertensive disorders and gestational diabetes for the mother and macrosomia and congenital abnormalities for the child. Previously, we demonstrated increases in inflammation, deficits in alveolarization, and decreases in angiogenic pathways in the offspring (PN21) of mice maintained on high fat diets during pregnancy and lactation. For the current studies we tested the hypothesis that maternal obesity would impair lung function in the offspring and that angiogenic pathways would continue to be depressed into adulthood (3 mon).MethodsFemale mice were fed high fat diets (HFD) or control diets (CD) for 8 weeks prior to mating and through weaning. At weaning the pups were placed on either CD or HFD until 3 months of age. Pulmonary function was assessed using a Scireq Flexivent. Expressions of angiogenic pathway proteins were measured by western blot in lung tissues.ResultsAt 3 months, pulmonary function tests indicated decreased inspiratory capacity, resistance (Rrs), elastance (Ers) and airway resistance (Rn) in the offspring that were fed HFD after weaning. These finding were exacerbated in pups having been born to and nursed by mothers fed HFD. Protein expression of PTP1B was also suppressed at 3 months.ConclusionsMaternal and adult HFD results in altered pulmonary function at 3 months of age. Changes in pulmonary function may contribute to increased morbidities associated with obesity.Support or Funding InformationThe authors gratefully acknowledge funding from the NIH/NICHD, R01HD0880833.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.