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

• Published in: Cardiovascular diabetology Vol. 18; no. 1; p. 165
• Main Authors: Shao, Qingmiao, Meng, Lei, Lee, Sharen, Tse, Gary, Gong, Mengqi, Zhang, Zhiwei, Zhao, Jichao, Zhao, Yungang, Li, Guangping, Liu, Tong
• Format: Journal Article
• Language: English
• Published: England BioMed Central 28.11.2019; BMC
• Subjects: Animal control; Animals; Atrial fibrillation; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Atrial Fibrillation - physiopathology; Atrial Fibrillation - prevention & control; Atrial Function, Left - drug effects; Atrial remodeling; Atrial Remodeling - drug effects; Benzhydryl Compounds - pharmacology; Blood pressure; Cholesterol; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - etiology; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetic rats; Diet, High-Fat; Digitization; Disease Models, Animal; Electron transport; Empagliflozin; Fibrillation; Fibrosis; Glucose; Glucose transporter; Glucosides - pharmacology; Heart rate; Heart Rate - drug effects; High fat diet; Laboratory animals; Low fat diet; Male; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondrial function; Mitochondrial Proteins - metabolism; Nutrient deficiency; Organelle Biogenesis; Original Investigation; Oxidative stress; Oxidative Stress - drug effects; Pathogenesis; Proteins; Rats, Sprague-Dawley; Respiratory function; Risk factors; SGLT-2 inhibitor; Signal Transduction; Sodium; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Streptozocin; Studies; Beijing China; United States > US; China; Diabetic rats; Empagliflozin; Atrial remodeling; Mitochondrial function; Atrial fibrillation; SGLT-2 inhibitor
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-019-0964-4

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. 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. 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. 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.