PMID- 36407026
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221122
IS  - 1726-9148 (Electronic)
IS  - 1726-913X (Print)
IS  - 1726-913X (Linking)
VI  - 20
IP  - 3
DP  - 2022 Jul
TI  - The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid 
      Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor alpha: 
      A Preclinical Study in Ovariectomized-Diabetic Rat Model.
PG  - e123560
LID - 10.5812/ijem-123560 [doi]
LID - e123560
AB  - 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 mug/Kg) was administrated for 6 weeks. Then, the levels of free fatty 
      acids (FFAs), CD36, peroxisome proliferator-activated receptor alpha (PPARalpha), 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 PPARalpha (P < 0.01) decreased in 
      T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARalpha, 
      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.
CI  - Copyright (c) 2022, International Journal of Endocrinology and Metabolism.
FAU - Jafarynezhad, Faezeh
AU  - Jafarynezhad F
AD  - Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of 
      Medical Sciences, Yazd, Iran.
FAU - Shahbazian, Mohammad
AU  - Shahbazian M
AD  - Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of 
      Medical Sciences, Yazd, Iran.
FAU - Farhadi, Zeinab
AU  - Farhadi Z
AUID- ORCID: 0000-0001-9718-8406
AD  - Department of Physiology, Faculty of Medicine, Kerman University of Medical 
      Sciences, Kerman, Iran.
FAU - Yadeghari, Maryam
AU  - Yadeghari M
AD  - Department of Anatomy and Cell Biology, Faculty of Medicine, Shahid Sadoughi 
      University of Medical Sciences, Yazd, Iran.
FAU - Rezvani, Mohammad Ebrahim
AU  - Rezvani ME
AUID- ORCID: 0000-0001-6146-806X
AD  - Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of 
      Medical Sciences, Yazd, Iran.
FAU - Safari, Fatemeh
AU  - Safari F
AUID- ORCID: 0000-0003-3943-8803
AD  - Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of 
      Medical Sciences, Yazd, Iran.
FAU - Azizian, Hossein
AU  - Azizian H
AUID- ORCID: 0000-0002-0921-094X
AD  - Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of 
      Medical Sciences, Yazd, Iran.
LA  - eng
PT  - Journal Article
DEP - 20220712
PL  - Netherlands
TA  - Int J Endocrinol Metab
JT  - International journal of endocrinology and metabolism
JID - 101235597
PMC - PMC9661540
OTO - NOTNLM
OT  - Cardiac
OT  - Diabetic Rats
OT  - GPER
OT  - Lipid
OT  - PPARalpha
COIS- Conflict of Interests: The authors declare no conflicts of interest.
EDAT- 2022/11/22 06:00
MHDA- 2022/11/22 06:01
PMCR- 2022/07/01
CRDT- 2022/11/21 04:27
PHST- 2022/02/26 00:00 [received]
PHST- 2022/06/11 00:00 [revised]
PHST- 2022/06/11 00:00 [accepted]
PHST- 2022/11/21 04:27 [entrez]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2022/11/22 06:01 [medline]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 10.5812/ijem-123560 [doi]
PST - epublish
SO  - Int J Endocrinol Metab. 2022 Jul 12;20(3):e123560. doi: 10.5812/ijem-123560. 
      eCollection 2022 Jul.