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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
J. Trnovska, P. Svoboda, H. Pelantova, M. Kuzma, H. Kratochvilova, BJ. Kasperova, I. Dvorakova, K. Rosolova, H. Malinska, M. Huttl, I. Markova, O. Oliyarnyk, M. Melcova, V. Skop, M. Mraz, S. Stemberkova-Hubackova, M. Haluzik
Language English Country Switzerland
Document type Journal Article
Grant support
GA19-06199S
Czech Science Foundation
IN 00023001
CZ - DRO ("Institute for Clinical and Experimental Medicine - IKEM")
NLK
Free Medical Journals
from 2000
Freely Accessible Science Journals
from 2000
PubMed Central
from 2007
Europe PubMed Central
from 2007
ProQuest Central
from 2000-03-01
Open Access Digital Library
from 2000-01-01
Open Access Digital Library
from 2007-01-01
Health & Medicine (ProQuest)
from 2000-03-01
ROAD: Directory of Open Access Scholarly Resources
from 2000
PubMed
34638943
DOI
10.3390/ijms221910606
Knihovny.cz E-resources
- MeSH
- Administration, Oral MeSH
- Benzhydryl Compounds administration & dosage MeSH
- 3T3-L1 Cells MeSH
- Hep G2 Cells MeSH
- Down-Regulation drug effects MeSH
- Dyslipidemias drug therapy MeSH
- Sodium-Glucose Transporter 2 Inhibitors administration & dosage MeSH
- Gluconeogenesis drug effects genetics MeSH
- Glucosides administration & dosage MeSH
- Weight Gain drug effects MeSH
- Hypertriglyceridemia drug therapy metabolism MeSH
- Hypoglycemic Agents administration & dosage MeSH
- Insulin Resistance MeSH
- Liver metabolism MeSH
- Rats MeSH
- Kidney metabolism MeSH
- Humans MeSH
- Lipogenesis drug effects genetics MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Oxidative Stress drug effects MeSH
- Cellular Senescence drug effects MeSH
- Adipose Tissue metabolism MeSH
- Up-Regulation drug effects MeSH
- Cell Survival drug effects MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
(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.
References provided by Crossref.org
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