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Maternal High Fat Diet Causes Decreased Alveolarization and Persistent Pulmonary Inflammation in the Offspring

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A7387 - Maternal High Fat Diet Causes Decreased Alveolarization and Persistent Pulmonary Inflammation in the Offspring
Author Block: L. K. Rogers1, K. Heyob2, S. Mieth3, T. E. Tipple4; 1Pediatrics, The Res Inst At Nationwide Childrens Hosp, Columbus, OH, United States, 2The Res Inst at Nationwide Childrens Hos, Columbus, OH, United States, 3The Res Inst At Nationwide Childrens Hosp, Columbus, OH, United States, 4Pediatrics / Neonatology, University of Alabama at Birmingham, Birmingham, AL, United States.
Background: The incidence of asthma and obesity continue to rise throughout the world. Past research has shown that obesity can exacerbate numerous pulmonary complications including severity of symptoms, treatment non-responsiveness, and required dosage for treatment efficacy. Maternal obesity has also been associated with multiple complications for both the mother and the child, including hypertensive disorders, diabetes, and chronic inflammation. We tested the hypothesis that maternal obesity would impair lung growth through a persistent inflammatory state. Methods: Female mice were fed high fat diets (HFD) or control diets (CD) for 8 weeks prior to mating and through weaning. Mouse pups were sacrificed at 21 days for inflammation analysis using PCR and western blot. An additional group of mouse pups were placed on CD or HFD at weaning and maintained until euthanized at 3 months. Pulmonary function tests were performed and lungs were either inflation fixed for morphometric analyses or frozen for biochemical assessment. Results: At 21 days, no differences were observed in IL-6, IL-5, TNF-alpha expression or pSMAD 2/3 protein levels in lung tissues. Higher protein levels of p65 and IKK, and lower levels of IkBalpha were observed in HFD compared to CD. pSTAT3, AKT, and pVEGFR2 protein levels were decreased in HFD. At 3 months, mice exposed to maternal HFD had fewer and larger alveoli than mice exposed to maternal CD. Decreases in PECAM protein levels were observed both by western blot and immunohistochemistry. Conclusions: Maternal HFD results in decreases in alveolarization, decreases in angiogenic signals and increases in NFkB signaling in the offspring.
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