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
| Author | Faezeh Jafarynezhad | en |
| Author | Mohammad Shahbazian | en |
| Author | Zeinab Farhadi | en |
| Author | Maryam Yadeghari | en |
| Author | Mohammad Ebrahim Rezvani | en |
| Author | Fatemeh Safari | en |
| Author | Hossein Azizian | en |
| Orcid | Zeinab Farhadi [0000-0001-9718-8406] | en |
| Orcid | Mohammad Ebrahim Rezvani [0000-0001-6146-806X] | en |
| Orcid | Fatemeh Safari [0000-0003-3943-8803] | en |
| Orcid | Hossein Azizian [0000-0002-0921-094X] | en |
| Issued Date | 2022-07-31 | en |
| Abstract | 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. | en |
| DOI | https://doi.org/10.5812/ijem-123560 | en |
| Keyword | GPER | en |
| Keyword | PPARα | en |
| Keyword | Cardiac | en |
| Keyword | Diabetic Rats | en |
| Keyword | Lipid | en |
| Publisher | Brieflands | en |
| Title | 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 | en |
| Type | Research Article | en |