Post-natal overfeeding influences both cardiomyocyte proliferation and lipid composition in juvenile mice

• Published in: Archives of cardiovascular diseases 2024-06, Vol.117 (6-7), p.S213-S213
• Main Authors: Josse, Marie, Rigal, Eve, Rosenblatt-Velin, Nathalie, Rochais, Francesca, Pais De Barros, Jean-Paul, Rochette, Luc, Vergely, Catherine
• Format: Article
• Language: English
• ISSN: 1875-2136; 1875-2128
• DOI: 10.1016/j.acvd.2024.05.109

Shortly after birth, the cardiac metabolism shifts from anaerobic glycolysis as the main energy source to predominantly utilizing mitochondrial fatty acid β-oxidation. Concomitantly, cardiomyocytes lose their ability to proliferate to switch towards a hypertrophic growth, but variations in the availability and utilization of metabolic substrates influences this post-natal proliferative window. Post-natal overfeeding (PNOF) induced by litter size reduction in rodents mimics the effect of childhood over-nutrition and induces disturbances in circulating metabolic substrates during adulthood. The aim of this study was to investigate post-natal cardiac proliferation and early lipid modifications in PNOF juvenile mice. C57BL/6 male pups were raised in litter adjusted to either 9 or 3 pups to form normally fed (NF) or post-natally overfed (PNOF) group, respectively. At 7, 10 and 24 days after birth (PN7, PN10 and PN24, respectively), hearts were harvested for immunostaining of the proliferation marker Ki67. Using liquid chromatography coupled to mass spectrometry, cardiac lipid composition was evaluated at PN7 and plasma lipidomic analysis was performed at PN7 and PN10. Finally, cardiomyocyte number was evaluated on Malassez counting chamber in PN24 hearts. Body weight and cardiac mass of PNOF pups were significantly higher than those of NF controls at all timepoints. At PN7, while circulating fatty acids remained unchanged, cardiolipin and fatty acid contents were significantly decreased in the hearts of PNOF pups. The lipid peroxidation products, oxysterols, HODE and HETE, were reduced in both plasma and the heart. At PN10, a decrease in circulating triglyceride levels was also observed. In parallel, at PN7, the proliferation rate of cardiomyocyte was significantly reduced and associated with an increase in cardiomyocyte surface. Finally, at PN24, a reduction of cardiomyocyte number was observed in PNOF mice. Shortly after birth, PNOF new-borns exhibit significant cardiac and plasma lipid changes. However, further investigations are needed to determine whether these modifications are associated with the shortening of post-natal cardiomyocyte proliferation, increased maturation, and consequently, the reduced cardiomyocyte number at weaning.