Consequences of a Maternal High-Fat Diet and Late Gestation Diabetes on the Developing Rat Lung

Autor: Muhammad Ali Khan, Peter F. Vitiello, Angela L. Wachal, Michelle L. Baack, Benjamin J. Forred, Danielle N. Jensen, Tricia D. Larsen
Rok vydání: 2016
Předmět:
0301 basic medicine
Lung Development
Organogenesis
Maternal Health
lcsh:Medicine
030204 cardiovascular system & hematology
Pulmonary function testing
Diagnostic Radiology
Rats
Sprague-Dawley
0302 clinical medicine
Endocrinology
Pregnancy
Medicine and Health Sciences
lcsh:Science
Lung
Multidisciplinary
Radiology and Imaging
Obstetrics and Gynecology
Pulmonary Imaging
3. Good health
Gestational diabetes
medicine.anatomical_structure
Pulmonary Veins
Prenatal Exposure Delayed Effects
Gestation
Female
Anatomy
Research Article
medicine.medical_specialty
Histology
Offspring
Endocrine Disorders
Death Rates
Imaging Techniques
Pulmonary Artery
Diet
High-Fat
Research and Analysis Methods
03 medical and health sciences
Vasculogenesis
Population Metrics
Diagnostic Medicine
Internal medicine
Diabetes mellitus
medicine
Diabetes Mellitus
Animals
Gestational Diabetes
Nutrition
Demography
Population Biology
business.industry
lcsh:R
Hemodynamics
Biology and Life Sciences
Maternal Nutritional Physiological Phenomena
medicine.disease
Rats
Diet
Pulmonary Alveoli
Diabetes
Gestational
030104 developmental biology
Animals
Newborn
Metabolic Disorders
People and Places
Women's Health
lcsh:Q
business
Organism Development
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 8, p e0160818 (2016)
ISSN: 1932-6203
Popis: Rationale Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development. Objective The objective of this study was to determine the effects of a maternal high-fat diet, alone and alongside late-gestation diabetes, on lung alveologenesis and vasculogenesis, as well as to ascertain if consequences persist beyond the perinatal period. Methods A rat model was used to study lung development in offspring from control, diabetes-exposed, high-fat diet-exposed and combination-exposed pregnancies via morphometric, histologic (alveolarization and vasculogenesis) and physiologic (echocardiography, pulmonary function) analyses at birth and 3 weeks of age. Outcomes were interrogated for diet, diabetes and interaction effect using ANOVA with significance set at p≤0.05. Findings prompted additional mechanistic inquiry of key molecular pathways. Results Offspring exposed to maternal diabetes or high-fat diet, alone and in combination, had smaller lungs and larger hearts at birth. High-fat diet-exposed, but not diabetes-exposed offspring, had a higher perinatal death rate and echocardiographic evidence of PPHN at birth. Alveolar mean linear intercept, septal thickness, and airspace area (D2) were not significantly different between the groups; however, markers of lung maturity were. Both diabetes-exposed and diet-exposed offspring expressed more T1α protein, a marker of type I cells. Diet-exposed newborn pups expressed less surfactant protein B and had fewer pulmonary vessels enumerated. Mechanistic inquiry revealed alterations in AKT activation, higher endothelin-1 expression, and an impaired Txnip/VEGF pathway that are important for vessel growth and migration. After 3 weeks, mortality remained highest and static lung compliance and hysteresis were lowest in combination-exposed offspring. Conclusion This study emphasizes the effects of a maternal high-fat diet, especially alongside late-gestation diabetes, on pulmonary vasculogenesis, demonstrates adverse consequences beyond the perinatal period and directs attention to mechanistic pathways of interest. Findings provide a foundation for additional investigation of preventative and therapeutic strategies aimed at decreasing pulmonary morbidity in at-risk infants.
Databáze: OpenAIRE
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