-
Something wrong with this record ?
Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet
S. Hojná, H. Malínská, M. Hüttl, Z. Vaňourková, I. Marková, D. Miklánková, J. Hrdlička, F. Papoušek, J. Neckář, P. Kujal, M. Behuliak, H. Rauchová, M. Kadlecová, D. Sedmera, K. Neffeová, E. Zábrodská, V. Olejníčková, J. Zicha, I. Vaněčková
Language English Country France
Document type Journal Article
- MeSH
- Benzhydryl Compounds * pharmacology MeSH
- Diet, High-Fat * adverse effects MeSH
- Sodium-Glucose Transporter 2 Inhibitors * pharmacology MeSH
- Glucosides * pharmacology MeSH
- Hypertension drug therapy MeSH
- Liver * drug effects metabolism pathology MeSH
- Cardiotonic Agents pharmacology MeSH
- Blood Glucose metabolism drug effects MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Kidney drug effects metabolism pathology MeSH
- Protective Agents pharmacology MeSH
- Rats, Inbred SHR * MeSH
- Fatty Liver prevention & control drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure. For the last two months, the rats were treated with empagliflozin (empa, 10 mg.kg-1.day-1 in the drinking water). Renal function and oral glucose tolerance test were analyzed in control (n=8), high-fat diet (SHR+HF, n=10), and empagliflozin-treated (SHR+HF+empa, n=9) SHR throughout the study. Metabolic parameters and echocardiography were evaluated at the end of the experiment. High-fat diet feeding increased body weight and visceral adiposity, liver triglyceride and cholesterol concentrations, and worsened glucose tolerance. Although the high-fat diet did not affect renal function, it significantly worsened cardiac function in a subset of SHR rats. Empagliflozin reduced body weight gain but not visceral fat deposition. It also improved glucose sensitivity and several metabolic parameters (plasma insulin, uric acid, and HDL cholesterol). In the liver, empagliflozin reduced ectopic lipid accumulation, lipoperoxidation, inflammation and pro-inflammatory HETEs, while increasing anti-inflammatory EETs. In addition, empagliflozin improved cardiac function (systolic, diastolic and pumping) independent of blood pressure. The results of our study suggest that hepatoprotection plays a decisive role in the beneficial effects of empagliflozin in preventing the progression of cardiac dysfunction induced by high-fat diet feeding.
1st Faculty of Medicine Charles University Prague Czech Republic
3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24014091
- 003
- CZ-PrNML
- 005
- 20250618083406.0
- 007
- ta
- 008
- 240725e20240405fr f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.biopha.2024.116520 $2 doi
- 035 __
- $a (PubMed)38581924
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a fr
- 100 1_
- $a Hojná, Silvie $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 245 10
- $a Hepatoprotective and cardioprotective effects of empagliflozin in spontaneously hypertensive rats fed a high-fat diet / $c S. Hojná, H. Malínská, M. Hüttl, Z. Vaňourková, I. Marková, D. Miklánková, J. Hrdlička, F. Papoušek, J. Neckář, P. Kujal, M. Behuliak, H. Rauchová, M. Kadlecová, D. Sedmera, K. Neffeová, E. Zábrodská, V. Olejníčková, J. Zicha, I. Vaněčková
- 520 9_
- $a A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure. For the last two months, the rats were treated with empagliflozin (empa, 10 mg.kg-1.day-1 in the drinking water). Renal function and oral glucose tolerance test were analyzed in control (n=8), high-fat diet (SHR+HF, n=10), and empagliflozin-treated (SHR+HF+empa, n=9) SHR throughout the study. Metabolic parameters and echocardiography were evaluated at the end of the experiment. High-fat diet feeding increased body weight and visceral adiposity, liver triglyceride and cholesterol concentrations, and worsened glucose tolerance. Although the high-fat diet did not affect renal function, it significantly worsened cardiac function in a subset of SHR rats. Empagliflozin reduced body weight gain but not visceral fat deposition. It also improved glucose sensitivity and several metabolic parameters (plasma insulin, uric acid, and HDL cholesterol). In the liver, empagliflozin reduced ectopic lipid accumulation, lipoperoxidation, inflammation and pro-inflammatory HETEs, while increasing anti-inflammatory EETs. In addition, empagliflozin improved cardiac function (systolic, diastolic and pumping) independent of blood pressure. The results of our study suggest that hepatoprotection plays a decisive role in the beneficial effects of empagliflozin in preventing the progression of cardiac dysfunction induced by high-fat diet feeding.
- 650 _2
- $a zvířata $7 D000818
- 650 12
- $a glukosidy $x farmakologie $7 D005960
- 650 12
- $a benzhydrylové sloučeniny $x farmakologie $7 D001559
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 12
- $a potkani inbrední SHR $7 D011918
- 650 12
- $a dieta s vysokým obsahem tuků $x škodlivé účinky $7 D059305
- 650 12
- $a játra $x účinky léků $x metabolismus $x patologie $7 D008099
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 12
- $a glifloziny $x farmakologie $7 D000077203
- 650 _2
- $a kardiotonika $x farmakologie $7 D002316
- 650 _2
- $a krevní tlak $x účinky léků $7 D001794
- 650 _2
- $a ledviny $x účinky léků $x metabolismus $x patologie $7 D007668
- 650 _2
- $a ztučnělá játra $x prevence a kontrola $x farmakoterapie $7 D005234
- 650 _2
- $a krevní glukóza $x metabolismus $x účinky léků $7 D001786
- 650 _2
- $a ochranné látky $x farmakologie $7 D020011
- 650 _2
- $a hypertenze $x farmakoterapie $7 D006973
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Malínská, Hana $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Hüttl, Martina $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Vaňourková, Zdeňka $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Marková, Irena $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Miklánková, Denisa $u Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Hrdlička, Jaroslav $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Papoušek, František $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Neckář, Jan $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 700 1_
- $a Kujal, Petr $u 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Behuliak, Michal $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic $7 xx0196023
- 700 1_
- $a Rauchová, Hana $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Kadlecová, Michaela $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Sedmera, David $u 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Neffeová, Kristýna $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Zábrodská, Eva $u 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Olejníčková, Veronika $u 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Zicha, Josef $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
- 700 1_
- $a Vaněčková, Ivana $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address: ivana.vaneckova@fgu.cas.cz
- 773 0_
- $w MED00005486 $t Biomedicine & pharmacotherapy $x 1950-6007 $g Roč. 174 (20240405), s. 116520
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38581924 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240725 $b ABA008
- 991 __
- $a 20250618083357 $b ABA008
- 999 __
- $a ok $b bmc $g 2143705 $s 1225957
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 174 $c - $d 116520 $e 20240405 $i 1950-6007 $m Biomedicine & pharmacotherapy $n Biomed Pharmacother $x MED00005486
- LZP __
- $a Pubmed-20240725
