Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

In-utero sucrose exposure increases risk of cardiac enlargement in C57BL6 mice offspring, regardless of postnatal diet. (#99)

Sophie Lucic Fisher 1 2 , Amanda Brandon 3 , Samantha Solon-Biet 2 , John O'Sullivan 1 3 4 , Yen Chin Koay 1 2 , Kim Bell-Anderson 3
  1. Cardiometabolic Medicine, School of Medical Sciences, Sydney, NSW, Australia
  2. Charles Perkins Centre, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia
  3. Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
  4. Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

It is well established that the in-utero environment can alter cardiometabolic risk later in life. One condition detected in-utero is Hypertrophic cardiomyopathy (HCM), characterised by abnormal thickening or enlargement of the heart muscle, the leading cause of sudden cardiac death. Dietary sugar consumption has been linked to HCM and glucose is the primary energy substrate for fetal growth. Previously, we have shown that fetal hearts from sucrose mothers were larger than those of chow mothers and had an increase in genes associated with one-carbon metabolism. To determine if this phenotype remained into adulthood, Female C57BL/6J mice were fed sucrose or AIN93G and mated. Pups (n=10 litters/group) either continued their mother’s diet or swapped to the other diet after birth. Body composition was determined by EchoMRI and hearts collected at 30-weeks of age for metabolomic analysis. At 30-weeks, female mice fed sucrose in-utero and swapped to AIN93G postnatally were smaller and had less fat than all other groups. Females fed sucrose only postnatally were heavier and fatter than mice fed only AIN93G. Male mice fed AIN93G in-utero and swapped to sucrose postnatally, were heavier and fatter than all other groups. Lifelong Sucrose-fed males were fatter than sucrose-AIN93G-fed mice. Female pups exposed to sucrose only in-utero had greater heart size than all other groups (p<0.001 AIN93G; p<0.001 sucrose; p<0.01 AIN93G-sucrose). Lifelong sucrose-fed females also had larger hearts than AIN93G mice (p<0.05). Male AIN93G-fed mice had smaller hearts than lifelong sucrose and sucrose-AIN93G mice (p<0.001 sucrose; p<0.05 sucrose-AIN93G mice). Additionally, lifelong sucrose-fed males had larger hearts than mice fed sucrose only postnatally (p<0.01). Metabolomics analysis showed interactions between in-utero sucrose exposure and the Methionine-Homocysteine cycle, folate metabolism, and one-carbon metabolism. While functional phenotype is still being established, these findings suggest that sucrose exposure in-utero, regardless of postnatal diet, increases risk of cardiac enlargement.