Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats

Cardiovascular Diabetology

Jichao Zhao¹  Sharen Lee²  Yungang Zhao³  Mengqi Gong⁴  Lei Meng⁴  Qingmiao Shao⁴  Gary Tse⁴  Zhiwei Zhang⁴  Guangping Li⁴  Tong Liu⁴ 

[1] Auckland Bioengineering Institute, The University of Auckland;Laboratory of Cardiovascular Physiology, Li Ka Shing Institute of Health Sciences;Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport;Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University;

关键词: Atrial fibrillation;    Empagliflozin;    SGLT-2 inhibitor;    Atrial remodeling;    Mitochondrial function;    Diabetic rats;   

DOI  :  10.1186/s12933-019-0964-4

来源: DOAJ

【 摘 要 】

Abstract Background Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

【 授权许可】

Unknown