P21 Western-diet induced obesity and cardiovascular pathophysiology is attenuated in male and female mice overexpressing Glutaredoxin-1

Hallmarks of obesity Western diets, include increased cardiac oxidative stress and cardiovascular diseases (CVDs) and are characterised by a high fat/high sucrose (HFHS) content. In CVD, oxidative post-translational modifications (oxPTM) like S-glutathionylation are known to play important roles. Glutaredoxin-1 (Grx1) which reverses S-glutathionylation is increased in CVD. Yet, the role of Grx1 overexpression in HFHS-induced obesity is unknown. This project aims to investigate the effect of HFHS diet-induced weight gain and cardiovascular pathophysiology in glutaredoxin-1 (Grx1Tg/+) overexpressing male and female mice. Male and female Grx1Tg/+ (TG) and wild-type (WT) littermates (8–12 weeks) were fed either normal chow (NC) or HFHS-diet for 10 weeks. EchoMRI was conducted before and after diet exposure, with body-weights measured weekly and. Aortic blood pressure (BP) and LV pressure-volume(PV) loops were obtained by retrogradely inserting a PV-catheter into the left ventricle (LV) after 10 weeks of diet. Ten-weeks of HFHS diet in both male and female WT mice increased bodyweight and% fat mass compared to TG mice. Following a HFHS-diet WT males had a higher% fat mass than WT females. Interestingly, HFHS increase in body weight and%-fat mass was attenuated in both male and female TG mice. Heart-rates were not significantly different between the groups and were close to physiological levels, allowing for reliable comparison of cardiac parameters. In WT mice, HFHS-diet increased diastolic and mean BP. However, no significant increase in DBP and MBP was observed in TG mice. In female TG mice, HFHS-diet reduced end diastolic volume, stroke volume and cardiac output compared to WT hearts. In conclusion, overexpression of Grx1 attenuated weight-gain and% fat mass. In accordance TG mice were protected against increased hypertension and cardiac dysfunction. Future studies are needed to identify the redox sensitive molecular pathways. This work was funded by Tenovus Scotland, T18–23.