533 - Combined Lipids and Antioxidants Promote Growth Factors and Biomarkers of Carbohydrate Metabolism During Neonatal Intermittent Hypoxia in Rats

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

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.