S-12-3: BENEFICIAL EFFECTS OF EMPAGLIFLOZIN ON METABOLIC PARAMETERS AND DIASTOLIC FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS FED A HIGH-FAT DIET

Abstract

Objective: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial pathological syndrome characterized by lipid accumulation in hepatocytes. This can lead to non-alcoholic steatohepatitis (NASH) which can progress to liver fibrosis, cirrhosis and liver cancer. Unfortunately, the pathogenesis of NAFLD is still unknown. However, current studies suggest that gliflozins, primarily antidiabetics, could have beneficial effects on liver metabolism. The aim of this study was therefore to examine whether empagliflozin (10 mg.kg-1.day-1 in drinking fluid) will have beneficial effects. Design and methods: NAFLD was induced by eight weeks of high-fat diet feeding (60% protein) in adult (6-month-old) spontaneously hypertensive rats (SHR). Control SHR were fed a standard diet. Then, the animals were either untreated or treated with empagliflozin for eight weeks. The evaluation of renal function (metabolic cages) and oral glucose tolerance (OGT) test were performed before the start of the treatment and at the end of the study. Cardiac function evaluated by echocardiography as well as metabolic parameters in serum and in liver were determined at the end of the experiment. Results: High-fat diet feeding increased body weight and visceral adiposity. Moreover, it worsened insulin resistance (evaluated as OGT test). In addition, it induced increase in triglycerides and cholesterol levels. Although it had no effect on renal function, it substantially deteriorated not only systolic but also diastolic function of the heart in SHR rats. Empagliflozin had no effect on body weight or visceral fat deposition but improved insulin sensitivity (OGT test) and several metabolic parameters (plasma insulin, non-esterified fatty acids, uric acid and HDL-cholesterol). Moreover, it had beneficial effects on systolic (fractional shortening) and especially diastolic (PWTd, RWT, and E/A ratio) function. Conclusions: Our results demonstrated that the treatment with empagliflozin had beneficial hepatoprotective and cardioprotective actions in hypertensive rats with experimentally induced non-alcoholic liver fatty disease.