(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

INTRODUCTION: Obesity and atrial fibrillation (AF) pose a significant burden on healthcare systems worldwide. Reduction of body weight has been documented to reduce the risk of AF. Little is known about the effect of different weight-reducing interventions including bariatric surgery in obese individuals on the risk of arrhythmia recurrence following catheter ablation (CA) for AF, and about the pathophysiological mechanisms linking these two conditions. METHODS: The Effect of complex weigHt-reducing interventiOns on rhythm control in oBese subjects wITh Atrial Fibrillation (HOBIT-AF) is a single-blinded, parallel-group randomised controlled trial with 18-month follow-up to assess the effect of complex weight-reducing interventions supported by the use of smart technologies and bariatric surgery on the arrhythmia burden in obese individuals following CA for AF. One hundred and sixty individuals (age 18-70 years, body mass index ≥ 30 kg/m2) will be randomised in a 1:1 fashion to undergo a structured weight reduction programme and sleeve gastrectomy (when indicated and preferred by the patient) aiming to achieve greater than 10% weight reduction from baseline (intervention group) or standard post-ablation medical care (control group). Two-week continuous ECG monitoring will be used 3 and 18 months after CA to assess the arrhythmia burden. Other investigations will include transthoracic echocardiography with quantification of epicardial adipose tissue, and markers of low-grade inflammation and circulating adipokines. PLANNED OUTCOMES: The main objective is to assess the effect of complex weight-reducing interventions on the arrhythmia burden and quality of life. Subgroup analyses to identify patient subgroups preferentially benefiting from weight loss related to a decrease in arrhythmia burden will be performed. Exploratory objectives will include investigation of potential mechanisms linking weight reduction with amelioration of arrhythmia burden such as changes in markers of low-grade inflammation, circulating adipokines, cytokines, monocytes or reduction of epicardial adipose tissue volume. TRIAL REGISTRATION: NCT04560387.

• Klíčová slova
• Atrial fibrillation, Bariatric surgery, Low-grade inflammation, Obesity, Sleeve gastrectomy, Weight reduction,
• MeSH
• dospělí MeSH
• fibrilace síní * komplikace   chirurgie   MeSH
• hmotnostní úbytek MeSH
• katetrizační ablace * MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita komplikace   chirurgie   MeSH
• randomizované kontrolované studie jako téma MeSH
• recidiva MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH