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Long-term metabolic effects of repeated neonatal oral sucrose treatment in mice

University of British Columbia

Background: Preterm infants (<37 weeks of gestation) often require hospitalization in the neonatal intensive care unit and experience painful procedures due to medical care. Oral sucrose treatment for analgesia is the non‑pharmacological standard of care for minor procedural pain relief. The objective of my MSc thesis research was to determine the long‑term effects of repeated neonatal oral sucrose treatment on growth, adiposity, and glucose homeostasis in a mouse model. Methodology: Neonatal female and male mice (C57BL/6J) were randomly assigned to one of four treatments (n=7‑10 mice/group/sex): water, sucrose, fructose, or glucose. Pups were treated 10 times/day for the first six days of life with 0.2g/kg body weight of respective treatments (24% solution; 1‑4 μL/dose) orally to model what is given to preterm infants. Mice were weaned onto a control diet and fed until age 16 weeks (adulthood). Pups were weighed daily from birth to weaning and weekly thereafter. Longitudinal growth and body composition were assessed at adulthood. Physiological assessments of glucose homeostasis (intraperitoneal glucose and insulin tolerance tests; glucose-stimulated insulin secretion test) were performed at weaning and adulthood. Insulin-like growth factor-1 (IGF-1) and liver water-soluble choline metabolites were also assessed. Results: Female and male sucrose-treated mice gained less weight during the suckling period (p<0.01 vs other groups) and were smaller at weaning compared to the water- and glucose-treated mice (p<0.05). At age 16 weeks, female sucrose-treated mice had smaller tibias (p<0.001 vs all) and lower serum IGF-1 concentrations (p<0.05 vs water). This was accompanied by lower (p<0.05 vs water) liver free choline, phosphocholine, and glycerophosphocholine concentrations, and higher betaine (p<0.01 vs water) concentrations in the sucrose-treated compared to the water-treated female mice. No differences in growth or liver choline metabolites were observed in male mice. Neonatal treatments had no effect on adiposity or glucose homeostasis in female or male mice. Conclusion: My findings suggest that repeated neonatal sucrose treatment affects growth in female mice, perhaps through an IGF‑1‑dependent pathway and alters liver choline metabolism. Further research is required to determine the functional consequences of these alterations.

Text

2020-05-04

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/74315

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/