(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.

• Klíčová slova
• cell senescence, empagliflozin, hereditary hypertriglyceridemic rat model, hypertriglyceridemia, insulin sensitivity, metabolic syndrome,
• MeSH
• aplikace orální MeSH
• benzhydrylové sloučeniny aplikace a dávkování   MeSH
• buňky 3T3-L1 MeSH
• buňky Hep G2 MeSH
• down regulace účinky léků   MeSH
• dyslipidemie farmakoterapie   MeSH
• glifloziny aplikace a dávkování   MeSH
• glukoneogeneze účinky léků   genetika   MeSH
• glukosidy aplikace a dávkování   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• hypertriglyceridemie farmakoterapie   metabolismus   MeSH
• hypoglykemika aplikace a dávkování   MeSH
• inzulinová rezistence MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• lipogeneze účinky léků   genetika   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• oxidační stres účinky léků   MeSH
• stárnutí buněk účinky léků   MeSH
• tuková tkáň metabolismus   MeSH
• upregulace účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny MeSH
• glukosidy MeSH
• hypoglykemika MeSH

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

• Klíčová slova
• cardiac surgery, coronary artery disease, diabetes mellitus, endoplasmic reticulum stress, epicardial fat, gene expression, inflammation, mitochondrial dysfunction,
• MeSH
• endoplazmatické retikulum genetika   metabolismus   MeSH
• exprese genu genetika   MeSH
• kosterní svaly metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mitochondrie genetika   metabolismus   MeSH
• myokard metabolismus   MeSH
• nemoci koronárních tepen genetika   patofyziologie   MeSH
• perikard metabolismus   MeSH
• podkožní tuk metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• stres endoplazmatického retikula genetika   fyziologie   MeSH
• transkriptom genetika   MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA MeSH