National Institute for Research of Metabolic and Cardiovascular Diseases
Published January 1, 2024 | Version v1
Journal article Open

Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet

Authors/Creators

  • 1. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
  • 2. Institut klinicke a experimentalni mediciny
  • 3. 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
  • 4. 1st Faculty of Medicine, Charles University, Prague, Czech Republic

Description

A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure. For the last two months, the rats were treated with empagliflozin (empa, 10 mg.kg-1.day-1 in the drinking water). Renal function and oral glucose tolerance test were analyzed in control (n=8), high-fat diet (SHR+HF, n=10), and empagliflozin-treated (SHR+HF+empa, n=9) SHR throughout the study. Metabolic parameters and echocardiography were evaluated at the end of the experiment. High-fat diet feeding increased body weight and visceral adiposity, liver triglyceride and cholesterol concentrations, and worsened glucose tolerance. Although the high-fat diet did not affect renal function, it significantly worsened cardiac function in a subset of SHR rats. Empagliflozin reduced body weight gain but not visceral fat deposition. It also improved glucose sensitivity and several metabolic parameters (plasma insulin, uric acid, and HDL cholesterol). In the liver, empagliflozin reduced ectopic lipid accumulation, lipoperoxidation, inflammation and pro-inflammatory HETEs, while increasing antiinflammatory EETs. In addition, empagliflozin improved cardiac function (systolic, diastolic and pumping) independent of blood pressure. The results of our study suggest that hepatoprotection plays a decisive role in the beneficial effects of empagliflozin in preventing the progression of cardiac dysfunction induced by high-fat diet feeding.

Notes

This study was supported by institutional support of the Institute of Physiology, Czech Academy of Sciences, grant Nr. RVO 67985823 and by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU. The study was also supported by grant no. NUJ21–02–00039 awarded to JH by the Grant Agency of the Ministry of Health of the Czech Republic. Finally, this work was also supported by the Ministry of Health of the Czech Republic - conceptual development of research organizations (Institute for Clinical and Experimental Medicine, IN 00023001).

Files

1-s2.0-S0753332224004049-main.pdf

Files (6.8 MB)

Name Size Download all
md5:e0057d0a7fd0c5e9382f4e70f0491040
6.8 MB Preview Download

Additional details

Related works

Has metadata
38581924 (PMID)
Is part of
0753-3322 (ISSN)
1950-6007 (ISSN)
References
10.1016/j.biopha.2024.116520 (DOI)