533 - Combined Lipids and Antioxidants Promote Growth Factors and Biomarkers of Carbohydrate Metabolism During Neonatal Intermittent Hypoxia in Rats
Friday, April 22, 2022
6:15 PM – 8:45 PM US MT
Poster Number: 533 Publication Number: 533.107
Despoina Myrsini Galetaki, State University of New York Downstate Medical Center College of Medicine, New York, NY, United States; Charles Cai, SUNY Downstate, BROOKLYN, NY, United States; Kulsajan S. Bhatia, State University of New York Downstate Medical Center College of Medicine, Brooklyn, NY, United States; Vivian L. Chin, SUNY Downstate, BROOKLYN, NY, United States; Jacob Aranda, State University of New York Downstate Medical Center College of Medicine, Brooklyn, NY, United States; Kay Beharry, State University of New York Downstate Medical Center College of Medicine, Brooklyn, NY, United States
Resident State University of New York Downstate Medical Center College of Medicine Brooklyn, New York, United States
Background: Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth requiring lipid supplementation. The growth hormone (GH)/insulin-like growth factor (IGF)-I system promotes growth and carbohydrate metabolism. GH interaction with its receptor induces IGF-I and leptin secretion which are important for growth and development.
Objective: We tested the hypothesis that early supplementation with lipids and/or antioxidants promote growth factors and biomarkers of carbohydrate metabolism in neonatal rats exposed to IH.
Design/Methods: Newborn rats (n=18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2), or room air (RA), from birth (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At P21, plasma samples were assessed for glucose, insulin, glucokinase (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), corticosterone, and ghrelin. Liver was assessed for histopathology, apoptosis (TUNEL stain), and growth hormone (GH), insulin-like growth factor (IGF)-I, GH binding protein (GHBP), and IGF binding protein (IGFBP)-3 using ELISA, Western blots, and immunohistochemistry (IHC).
Results: Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10+fish oil, while corticosterone was higher with nGSH and CoQ10+fish oil. In the liver, IGF-I and IGFBP-3 were significantly higher with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10+fish oil reduced IGF-I in RA and IH, but increased IGFBP-3.Conclusion(s): Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, fish oil, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and GH/IGF system. Data suggest that these supplements may improve poor postnatal organ and body growth, as well as metabolic dysfunction associated with neonatal IH.