Empagliflozin attenuates liver steatosis and improves cardiac complications in choline-deficient high-fat diet-induced MAFLD rats.

Growing evidence suggests a strong relation between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease (CVD). Limited approaches are available to reduce CVD risk in MAFLD. Recent evidence suggests that Sodium-glucose transporter 2 (SGLT2) inhibitors represent a promising class of drugs for managing MAFLD. Here, we aim to observe the effect of the SGLT2 inhibitor, empagliflozin, on heart and liver function in MAFLD. To induce MAFLD, Sprague-Dawley (SD) Rats were divided into three groups: the CDHF group fed a choline-deficient high-fat (CDHF) diet, the CDHF + EMP group fed with CDHF plus a daily dose of 10 mg/kg/day empagliflozin orally, and the control group fed with a chow diet till 20 weeks. After 20 weeks of empagliflozin treatment, MAFLD rats showed an anti-steatosis effect in the liver, measured by histopathology and ultrasound imaging. Further, empagliflozin has reduced the insulin resistance and dyslipidemia in CDHF diet-fed MAFLD rats compared to the control. Empagliflozin improved the echocardiography of the MAFLD rat hearts by decreasing the elevated left ventricular (LV) mass, LV anterior and posterior wall thickness, ejection fraction, and fractional shortening. In addition, empagliflozin significantly increased the decreased diastolic diameter and volume, and decreased the elevated QRS interval in MAFLD rats compared to controls. Further, histopathology showed the presence of fibrosis and intracytoplasmic vacuolation in cardiomyocytes of MAFLD, which has been effectively reduced after empagliflozin treatment. In conclusion, empagliflozin could be a potential therapeutic strategy to prevent the MAFLD and associated cardiac complications by improving fat accumulation in the liver and normalizing cardiac function.