Empagliflozin alters lipid metabolism in the myocardium and liver in a prediabetes model with severe dyslipidemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00084950" target="_blank" >RIV/00023001:_____/24:00084950 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10483221

Výsledek na webu

<a href="https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1393946/full" target="_blank" >https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1393946/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2024.1393946" target="_blank" >10.3389/fphar.2024.1393946</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Empagliflozin alters lipid metabolism in the myocardium and liver in a prediabetes model with severe dyslipidemia

Popis výsledku v původním jazyce

Background and aims Recent studies suggest that empagliflozin reduces total and cardiovascular mortality in both diabetic and nondiabetic subjects. Although the exact mechanism is unclear, it is understood to positively affect myocardial energetics, including the metabolism of ketone bodies, lipids, and fatty acids. In this study, we compared empagliflozin effects on lipid metabolism in the heart and liver in a prediabetic rat model with severe dyslipidemia. Materials and methods Wistar rats served as the control group, while hereditary hypertriglyceridemic (HHTg) rats were used as a nonobese, prediabetic model. Rats were treated with or without empagliflozin at a dose of 10 mg/kg body weight (BW) for 8 weeks. Results In HHTg rats, empagliflozin decreased body weight and adiposity, improved glucose tolerance, and decreased serum triacylglycerols (TAGs) (p &lt; 0.001). Empagliflozin decreased the activity and gene expression of the lipogenic enzyme SCD-1 (p &lt; 0.001) in the myocardium, which may have led to a decrease in the ectopic accumulation of TAGs and lipotoxic diacylglycerols and lysophosphatidylcholines (p &lt; 0.001). Changes in the myocardial phosphatidylcholine/phosphatidylethanolamine ratio (p &lt; 0.01) and in the fatty acid profile of myocardial phospholipids may have contributed to the antifibrotic effects of empagliflozin. The anti-inflammatory effects of empagliflozin were evidenced by an increased IL-10/TNF alpha ratio (p &lt; 0.001), a marked decrease in arachidonic acid metabolites (20-HETE, p &lt; 0.001), and an increase in PUFA metabolites (14,15-EETs, p &lt; 0.001) in the myocardium. However, empagliflozin did not significantly affect either the concentration or utilization of ketone bodies. In the liver, empagliflozin decreased lipogenesis and the accumulation of TAGs and lipotoxic intermediates. Its effect on arachidonic acid metabolites and alterations in n-3 PUFA metabolism was less pronounced than in the myocardium. Conclusion Our findings suggest that empagliflozin treatment in the heart and liver reduced the accumulation of neutral lipids and lipotoxic intermediates and altered the metabolism of n-3 PUFA. In the heart, empagliflozin altered arachidonic acid metabolism, which is likely associated with the anti-inflammatory and antifibrotic effects of the drug. We assume that these alterations in lipid metabolism contribute to the cardioprotective effects of empagliflozin in prediabetic states with severe dyslipidemia.

Název v anglickém jazyce

Empagliflozin alters lipid metabolism in the myocardium and liver in a prediabetes model with severe dyslipidemia

Popis výsledku anglicky

Background and aims Recent studies suggest that empagliflozin reduces total and cardiovascular mortality in both diabetic and nondiabetic subjects. Although the exact mechanism is unclear, it is understood to positively affect myocardial energetics, including the metabolism of ketone bodies, lipids, and fatty acids. In this study, we compared empagliflozin effects on lipid metabolism in the heart and liver in a prediabetic rat model with severe dyslipidemia. Materials and methods Wistar rats served as the control group, while hereditary hypertriglyceridemic (HHTg) rats were used as a nonobese, prediabetic model. Rats were treated with or without empagliflozin at a dose of 10 mg/kg body weight (BW) for 8 weeks. Results In HHTg rats, empagliflozin decreased body weight and adiposity, improved glucose tolerance, and decreased serum triacylglycerols (TAGs) (p &lt; 0.001). Empagliflozin decreased the activity and gene expression of the lipogenic enzyme SCD-1 (p &lt; 0.001) in the myocardium, which may have led to a decrease in the ectopic accumulation of TAGs and lipotoxic diacylglycerols and lysophosphatidylcholines (p &lt; 0.001). Changes in the myocardial phosphatidylcholine/phosphatidylethanolamine ratio (p &lt; 0.01) and in the fatty acid profile of myocardial phospholipids may have contributed to the antifibrotic effects of empagliflozin. The anti-inflammatory effects of empagliflozin were evidenced by an increased IL-10/TNF alpha ratio (p &lt; 0.001), a marked decrease in arachidonic acid metabolites (20-HETE, p &lt; 0.001), and an increase in PUFA metabolites (14,15-EETs, p &lt; 0.001) in the myocardium. However, empagliflozin did not significantly affect either the concentration or utilization of ketone bodies. In the liver, empagliflozin decreased lipogenesis and the accumulation of TAGs and lipotoxic intermediates. Its effect on arachidonic acid metabolites and alterations in n-3 PUFA metabolism was less pronounced than in the myocardium. Conclusion Our findings suggest that empagliflozin treatment in the heart and liver reduced the accumulation of neutral lipids and lipotoxic intermediates and altered the metabolism of n-3 PUFA. In the heart, empagliflozin altered arachidonic acid metabolism, which is likely associated with the anti-inflammatory and antifibrotic effects of the drug. We assume that these alterations in lipid metabolism contribute to the cardioprotective effects of empagliflozin in prediabetic states with severe dyslipidemia.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5104" target="_blank" >LX22NPO5104: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in pharmacology [online]

ISSN

1663-9812

e-ISSN

1663-9812

Svazek periodika

15

Číslo periodika v rámci svazku

July 4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

"art. no. 1393946"

Kód UT WoS článku

001271852600001

EID výsledku v databázi Scopus

2-s2.0-85198746206