the g-protein-coupled estrogen receptor agonist prevents cardiac lipid accumulation by stimulating cardiac peroxisome proliferator-activated receptor α: a preclinical study in ovariectomized-diabetic rat model

Background: type 2 diabetes mellitus (t2dm) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (cvds). the g protein-coupled estrogen receptor (gper), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both t2dm and menopause, but its mechanism of action is not well understood. objectives: this study aimed to determine whether g1 as a selective gper-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with t2dm. methods: female wistar rats were divided into 5 groups (n = 7 in each group): sham-control (sh-ctl), t2dm, ovariectomized-t2dm (ovx-t2dm), ovx-t2dm-g1 (gper-agonist), and ovx-t2dm-vehicle (ovx-t2dm-veh). after stabilization of t2dm, g1 (200 μg/kg) was administrated for 6 weeks. then, the levels of free fatty acids (ffas), cd36, peroxisome proliferator-activated receptor α (pparα), and lipid accumulation in the cardiac tissue were determined. results: compared with the sh-ctl group, cardiac ffas (p < 0.001), cd36 (p < 0.05), and lipid accumulation (p < 0.001) increased, and cardiac pparα (p < 0.01) decreased in t2dm animals; ovariectomy intensified these changes. also, cardiac ffas, pparα, and lipid accumulation (p < 0.05) significantly decreased in the ovx-t2dm-g1 group compared to the ovx-t2dm-veh group. however, cardiac cd36 levels did not change. conclusions: g1 as a selective gper-agonist affects lipid metabolism in t2dm animals. it also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.