{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:24:33Z","timestamp":1789698273241,"version":"4.0.1"},"reference-count":84,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["GA19-06199S"],"award-info":[{"award-number":["GA19-06199S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CZ - DRO (\u201eInstitute for Clinical and Experimental Medicine \u2013 IKEM\u201c)","award":["IN 00023001"],"award-info":[{"award-number":["IN 00023001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: empagliflozin, sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an effective antidiabetic agent with strong cardio- and nephroprotective properties. The mechanisms behind its cardio- and nephroprotection are still not fully clarified. (2) Methods: we used male hereditary hypertriglyceridemic (hHTG) rats, a non-obese model of dyslipidaemia, insulin resistance, and endothelial dysfunction fed standard diet with or without empagliflozin for six weeks to explore the molecular mechanisms of empagliflozin effects. Nuclear magnetic resonance (NMR)-based metabolomics; quantitative PCR of relevant genes involved in lipid and glucose metabolism, or senescence; glucose and palmitic acid oxidation in isolated tissues and cell lines of adipocytes and hepatocytes were used. (3) Results: empagliflozin inhibited weight gain and decreased adipose tissue weight, fasting blood glucose, and triglycerides and increased HDL-cholesterol. It also improved insulin sensitivity in white fat. NMR spectroscopy identified higher plasma concentrations of ketone bodies, ketogenic amino acid leucine and decreased levels of pyruvate and alanine. In the liver, adipose tissue and kidney, empagliflozin up-regulated expression of genes involved in gluconeogenesis and down-regulated expression of genes involved in lipogenesis along with reduction of markers of inflammation, oxidative stress and cell senescence. (4) Conclusion: multiple positive effects of empagliflozin, including reduced cell senescence and oxidative stress, could contribute to its long-term cardio- and nephroprotective actions.<\/jats:p>","DOI":"10.3390\/ijms221910606","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"10606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in the Liver, Kidney and Adipose Tissue of Hereditary Hypertriglyceridemic Rats: Possible Contribution of Attenuation of Cell Senescence and Oxidative Stress"],"prefix":"10.3390","volume":"22","author":[{"given":"Jaroslava","family":"Trnovska","sequence":"first","affiliation":[{"name":"Cardiometabolic Research Division, Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech 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Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Stemberkova-Hubackova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Therapy, Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Haluzik","sequence":"additional","affiliation":[{"name":"Diabetes Centre, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic"},{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, 128 08 Prague, Czech 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