Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet
Language English Country France Media print-electronic
Document type Journal Article
PubMed
38581924
DOI
10.1016/j.biopha.2024.116520
PII: S0753-3322(24)00404-9
Knihovny.cz E-resources
- Keywords
- Cardiac function, Kidney function, Liver steatosis, Metabolic parameters, SGLT-2 inhibition,
- MeSH
- Benzhydryl Compounds * pharmacology MeSH
- Diet, High-Fat * adverse effects MeSH
- Sodium-Glucose Transporter 2 Inhibitors * pharmacology MeSH
- Glucosides * pharmacology MeSH
- Hypertension drug therapy MeSH
- Liver * drug effects metabolism pathology MeSH
- Cardiotonic Agents pharmacology MeSH
- Blood Glucose metabolism drug effects MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney drug effects metabolism pathology MeSH
- Protective Agents pharmacology MeSH
- Rats, Inbred SHR * MeSH
- Fatty Liver prevention & control drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Benzhydryl Compounds * MeSH
- empagliflozin MeSH Browser
- Sodium-Glucose Transporter 2 Inhibitors * MeSH
- Glucosides * MeSH
- Cardiotonic Agents MeSH
- Blood Glucose MeSH
- Protective Agents MeSH
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 anti-inflammatory 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.
1st Faculty of Medicine Charles University Prague Czech Republic
3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
References provided by Crossref.org
Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases
