Maternal and offspring high-fat diet leads to platelet hyperactivation in male mice offspring

Renato S Gaspar,Roger D Cox,Alexander P Bye,Craig E Hughes,Dyan Sellayah,Amanda J Unsworth,Michelle Stewart,Jonathan M Gibbins,Alaa Al-Dibouni,Sara Wells,Tanya Sage

doi:10.1038/s41598-020-80373-3

Renato S Gaspar, Roger D Cox + Show 9 more

Open Access

https://doi.org/10.1038/s41598-020-80373-3

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Abstract

Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact on platelet physiology has not been studied. Here, we examined whether maternal high-fat diet (HF) ingestion affects the platelet function in lean and obese offspring. C57BL6/N mice dams were given a HF or control (C) diet for 8 weeks before and during pregnancy. Male and female offspring received C or HF diets for 26 weeks. Experimental groups were: C/C, dam and offspring fed standard laboratory diet; C/HF dam fed standard laboratory diet and offspring fed HF diet; HF/C and HF/HF. Phenotypic and metabolic tests were performed and blood collected for platelet studies. Compared to C/C, offspring HF groups were obese, with fat accumulation, hyperglycaemia and insulin resistance. Female offspring did not present platelet hyperactivity, hence we focused on male offspring. Platelets from HF/HF mice were larger, hyperactive and presented oxidative stress when compared to C/C. Maternal and offspring HF diet results in platelet hyperactivation in male mouse offspring, suggesting a novel ‘double-hit’ effect.

Highlights

Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring
Both offspring high-fat diet (HF) groups presented significant increases in body weight, fat mass, total cholesterol, fasting glucose, TyG Index which is a surrogate for insulin resistance, as well as HDL and LDL levels when compared to offspring C groups
This study describes the impact of maternal obesity during pregnancy in mice on the platelet activity of offspring

Summary

Introduction

Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. This concept of developmental programming of cardiovascular disease has since been expanded to include maternal over-nutrition, which is more reflective of Western lifestyles Both epidemiological and animal studies have established unequivocally that maternal diabetes, obesity or maternal high-fat (HF) diet during pregnancy is associated with increased susceptibility to cardiovascular disease in offspring (reviewed by Williams et al.4), the precise mechanisms underlying this observation remain to be established. From a clinical perspective their major role is at the later stages of disease when platelets can form unwanted thrombi on atherosclerotic plaques, or when unstable plaques rupture These acute thrombotic events cause stenosis or occlusion of vessels supplying the heart or brain resulting in myocardial infarction (MI) or stroke respectively (for review see[8]). A recent cohort study has documented that increased platelet activation in participants before the onset of cardiovascular disease, was a major risk factor and predictor for myocardial infarction and stroke events later in life[9]

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