Research Associate Memorial University of Newfoundland St. John's, Newfoundland and Labrador, Canada
Disclosure(s):
Olupathage C. Dinesh, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Mice lacking Bco2, the sole β-carotene (BC) cleavage enzyme expressed in adult heart, show reduced retinoic acid (RA), a metabolite of vitamin A (VA) and reduced pyruvate dehydrogenase kinase (Pdk) 4 expression as well as increased pyruvate dehydrogenase (PDH) activity and reprogramming of fuel preference (glucose over fat) in their heart. Neonatal piglets on Parenteral Nutrition (PN) show altered lipid metabolism. Fetus and healthy neonates receive retinyl palmitate (vitamin A ester; RP) and BC through placenta and the mother’s milk, respectively. PN is devoid of BC, the sole VA source during PN is RP. Despite RP supplementation during PN, premature neonates experience a wide variation and below normal levels of serum VA. In dams given sufficient VA, a single dose of BC upregulated embryonic Bco2. Moreover, RA given to embryonic cardiomyocyte increased Pdk4 expression and reduced the activity of PDH complex, a key regulators of cardiac fuel utilization. Hypothesis: absence of BC in premature PN will alter cardiac reprogramming for fuel preferences (glucose over lipid).
Objective: investigate if BC supplementation to premature pups improves cardiac RA, Bco2 and Pdk4 mRNAs, PDH activity and triglycerides (TG) and essential fatty acids (EFAs).
Methods: 2 cohort of premature pups (postnatal day 4) from C57BL6 dams will receive: RP + BC or RP + vehicle for 14 days with mouse milk substitute. Cardiac Bco2, Pdk4 mRNA will be visualized (RNAScope). Cardiac PDH activity, serum and cardiac BC, RA, TG and EFAs will be compared.
Results: N/A
Conclusions: Immune staining of mRNAs of Bco2 and Pdk4 will allow us to understand early epigenetic modifications even before beginning to see changes to actual proteins or metabolism. Increased PDH activity, altered EFAs composition and TG in cardiac tissues will suggest metabolic shift in premature neonates which are prodromal to later metabolic syndrome. Results will expand the knowledge of BC as a potential contributor to adult heart health at a very early stage.
References: Holloway C et al. Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: FASEB J. 2022.
Wassef L et al. High Preformed Vitamin A Intake during Pregnancy Prevents Embryonic Accumulation of Intact β-Carotene from the Maternal Circulation in Mice. J Nutr. 2015.
