Maternal high fat high energy diet reduces thyroid hormone concentrations and markers of growth in the nonhuman primate fetal heart — ASN Events

Maternal high fat high energy diet reduces thyroid hormone concentrations and markers of growth in the nonhuman primate fetal heart (#323)

Melanie Bertossa 1 , Bianca Cam 1 , Ashley Meakin 1 , Stacey Holman 1 , Michael Wiese 1 , Peter Nathanielsz 2 , Janna Morrison 1
  1. Health and Biomedical Innovation, School of Pharmacy and Biomedical Science, Early Origins of Adult Health Research Group, Robinson Research Institute, Adelaide University, Adelaide , South Australia , Australia
  2. Texas Center for Pregnancy and Life Course Health, Southwest National Primate Research Institute, Texas Biomedical Research Institute, San Antonio, Texas, United States

Maternal high fat-high energy diets (HF-HEDs) are prevalent, and offspring are at risk of cardiovascular disease (CVD). However, the underlying mechanism(s) are unclear. The rise in thyroid hormones (TH) during late gestation triggers maturation of cardiac growth. We aimed to determine how maternal HF-HED impacts TH concentrations and markers of cardiac growth in the baboon fetal heart.

Female baboons of similar weight were randomly assigned to a control diet (n=12, 6 females (f), 6 males (m)); metabolizable energy content (MEC)=3.07kcal/g, 12% fat) or a HF-HED (n=12, 6f, 6m)); MEC=4.03kcal/g, 45% fat) ~9 months prior to and during pregnancy. At 0.9 gestation, fetuses were delivered by Caesarean section and humanely killed whilst under general anesthesia. Fetal cardiac left ventricle (LV) samples were collected. Gene expression was measured via qPCR, protein abundance via Western blot and tissue thyroid hormone (Triiodothyronine (T3) and Thyroxine (T4)) concentration via liquid chromatography-tandem mass spectrometry. Data was analysed via a two-way ANOVA (factors: diet and sex) followed by a Bonferroni post hoc test. P<0.05 considered statistically significant.

Maternal HF-HED decreased fetal cardiac concentrations of T3 (P=0.016). Cardiac mRNA expression of insulin-like growth factor (IGF) 2 and receptors, IGF1R and IGF2R, were reduced in both HF-HED sexes compared to Controls (Pdiet= 0.0186; 0.011; 0.033 respectively). Proliferative cellular nuclear antigen (PCNA) was reduced in both HF-HED sexes compared to Controls (Pdiet= 0.021). PCNA was negatively associated with cardiac T3:T4 concentration (P=0.016, R2=0.720). Akt abundance was reduced in HF-HED females compared to Control females (Pint=0.008). The abundance of apoptosis marker p53 was increased in HF-HED males compared to Control males (Pint=0.0003).

Maternal HF-HED suppressed growth markers, influenced by hormonal cues and likely contributes to the early origins of CVD. Targeting these mechanisms/promoting good maternal nutrition may prevent the fetal origins of CVD and reduce burden.