Empagliflozin (EMPAG), an SGLT2 inhibitor, improves glucose metabolism by increasing urinary glucose output. EMPA-REG OUTCOME study documented cardiovascular (CV) benefits of EMPAG in patients with type 2 diabetes (T2DM) and history of a CV event. This work was undertaken to investigate complex effects of EMPAG in hereditary hypertriglyceridemic rats (HHTg), a non-obese, nondiabetic model of metabolic sydrome. HHTg rats are characterized by the presence of dyslipidemia and insulin resistance without obesity or hyperglycemia. 8 months old male HHTg rats were fed a standard diet (SD) or SD enriched by EMPAG in a dose of 10 mg/kg body weight/day for 6 weeks. EMPAG treatment suppressed an increase in body weight despite greater average food intake in EMPAG relative to control group. EMPAG administration induced glycosuria (+99%; P<0.001) and decreased fasting glycemia (-21%; P<0.02). Plasma lipid profile in postprandial state revealed a decrease in triglycerides (-34%; P<0.001) and insulin (-36%;P<0.01), increase in HDL cholesterol (+17%; P<0.01) and free fatty acids (+36%; P<0.02). Systemic ketone bodies concentrations were unchanged with simultaneous decrease in 14C-palmitic acid oxidation in the myocardium suggesting ketone bodies utilization by this tissue. EMPAG improved parameters of oxidative stress (SOD: +24%; P<0.03; GSH-Px: +31%; P<0.01; TBARS: -17%; P<0.003) in the kidney and decreased glycogen content in the liver and muscle by 39% and 13%; respectively (P<0.01). EMPAG improved insulin sensitivity of white adipose tissue (+13%; P<0.05) and decreased relative weight of perirenal adipose tissue (-13%; P<0.01).

In conclusion, in nondiabetic rats with MS, EMPAG improved insulin sensitivity of WAT, dyslipidemia and oxidative stress in the kidney. Combination of these factors may partially explain CV benefits of EMPAG in T2DM and suggests the possibility of similar benefits in patients with metabolic syndrome without diabetes.


J. Trnovska: None. M. Hüttl: None. I. Marková: None. O. Oliyarnyk: None. H. Malinska: None. L. Kazdova: None. M. Haluzik: None.

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