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

0551577 - MBÚ 2022 RIV CH eng J - Journal Article
Trnovská, J. - Svoboda, P. - Pelantová, Helena - Kuzma, Marek - Kratochvílová, H. - Kasperova, B. - Dvořáková, I. - Rosolová, K. - Malínská, H. - Hüttl, M. - Marková, I. - Oliyarnyk, O. - Melčová, M. - Skop, V. - Mráz, M. - Štemberková-Hubáčková, Soňa - Haluzík, M.
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.
International Journal of Molecular Sciences. Roč. 22, č. 19 (2021), č. článku 10606. E-ISSN 1422-0067
Institutional support: RVO:61388971 ; RVO:86652036
Keywords : empagliflozin * metabolic syndrome * hypertriglyceridemia * insulin sensitivity * cell senescence * hereditary hypertriglyceridemic rat model
OECD category: Microbiology; Biochemistry and molecular biology (BTO-N)
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/19/10606

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.
Permanent Link: http://hdl.handle.net/11104/0326848