Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB047

Poster Communications

Effects of maternal high fat diet and metformin treatment on adult mouse offspring cardiac ventricle wall thickness

M. G. Hosken1, S. A. Lanham1, H. Thomas1, F. R. Cagampang1, L. R. Green1

1. Institute of Developmental Sciences, University of Southampton, Southampton, United Kingdom.

Maternal obesity and high-fat (HF) diet is associated with fetal myocardial thickening and contractile dysfunction, and with adult offspring hypertension and insulin resistance (1-3). These early life effects of HF may influence the risk of disease in a subsequently obesogenic adult environment. The insulin-sensitising drug metformin is linked to improved cardiac function (4), and it is prescribed for use in diabetic pregnancies. In mature adult mouse offspring, we determined the interactive effect of maternal and post-weaning HF diet on left ventricular wall thickness (LVWT), a risk factor for cardiovascular disease, and the effect of maternal metformin treatment. C57/BL6J female mice received a control (C, 7% kcal fat) or HF (45% kcal fat) diet 6 weeks pre-mating, and throughout pregnancy and lactation. Half of the dams were given metformin (m) in drinking water (250mg/kg bodyweight/day) throughout pregnancy and lactation. Male and female offspring were weaned onto the C or HF diet until they were killed at 30 weeks old, creating 8 diet groups: C/C, C/HF, HF/C, HF/HF, Cm/C, Cm/HF, HFm/C, HFm/HF (n=5-10 per sex per group). The LVWT was determined in three-dimensional images by microcomputed tomography of paraffin-embedded ventricles (SkyScan, Bruker). Data were analysed by 2-way ANOVA. In females and males, LVWT per gram heart weight was decreased in HF/C vs. C/C offspring (female, 8.08±0.60 vs. 10.70±0.70, p<0.001; male, 8.14±0.39 vs. 9.44±0.37, p<0.01). With maternal metformin treatment, these effects were no longer apparent. In contrast to immature offspring (1,2), a thinner left ventricular wall relative to heart size was observed in older offspring of HF fed mothers. Amelioration of this effect by maternal metformin treatment could be due to its insulin sensitizing actions, or via cardiac-specific AMPK activation (4). These novel findings have potential implications for minimizing cardiovascular risk in offspring of obese pregnancies.

Where applicable, experiments conform with Society ethical requirements