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

Result code in 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>

Alternative codes found

RIV/00216208:11110/24:10483221

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LX22NPO5104" target="_blank" >LX22NPO5104: National Institute for Research of Metabolic and Cardiovascular Diseases</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Frontiers in pharmacology [online]

ISSN

1663-9812

e-ISSN

1663-9812

Volume of the periodical

15

Issue of the periodical within the volume

July 4

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

"art. no. 1393946"

UT code for WoS article

001271852600001

EID of the result in the Scopus database

2-s2.0-85198746206