Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia-Reperfusion Injury in Zucker Rats

Janis Kuka (Coresponding Author), Marina Makrecka-Kuka, Karlis Vilks, Stanislava Korzh, Helena Cirule, Eduards Sevostjanovs, Solveiga Grinberga, Maija Dambrova, Edgars Liepinsh

Research output: Contribution to journalArticlepeer-review

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Abstract

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl-GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long-chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.

Original languageEnglish
Article number7493190
Number of pages13
JournalOxidative Medicine and Cellular Longevity
Volume2021
DOIs
Publication statusPublished - 29 Jul 2021

Field of Science*

  • 1.4 Chemical sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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