Long-chain acylcarnitines: from mitochondrial metabolism to clinical applications

Edgars Liepiņš, Maija Dambrova

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Properly functioning mitochondria are critical for sufficient ATP production in every cell. A lower number, inadequate performance and damaged membranes of mitochondria result in various diseases. Carnitine palmitoyltransferase 1 (CPT 1)-mediated long-chain acylcarnitine synthesis is a step in mitochondrial fatty acid (FA) oxidation. Various mitochondrial disorders are characterized by incomplete FA oxidation and following accumulation of long-chain acylcarnitines. In this case, the highest concentrations of long-chain acylcarnitines are found in the mitochondrial inner membrane and the intermembrane space. In cardiac mitochondria, long-chain acylcarnitines inhibit pyruvate and lactate metabolism even at physiological concentrations. At elevated levels, the accumulation of long-chain acylcarnitines inhibits OXPHOS, inducing mitochondrial membrane hyperpolarization, and stimulating production of reactive oxygen species. Thus, the high mitochondrial content of long-chain acylcarnitines could increase the risk of mitochondrial and cardiac damage, particularly in conditions of cardiac ischemia. Decreasedlong-chain acylcarnitine synthesis has been confirmed as a promising approach in various disease models including myocardial infarction, atherosclerosis, and insulin resistance. In recent studies, a pharmacological decrease of long-chain acylcarnitines is studied in models of cardiometabolic diseases, inherited disorders, cancer, endotoxemia- and pulmonary hypertrophy-induced cardiac damage opening new horizons for long-chain acylcarnitine-lowering and mitochondria-protective strategies. Long-chain acylcarnitine measurements in the fasted state are appropriate for the assessment of mitochondrial function, while insulin resistance can be detected only in the postprandial state after a controlled glucose load. In a recent study, we tested whether a decrease in circulating long-chain acylcarnitine concentrations after glucose administration in a glucose tolerance test is associated with insulin sensitivity and can be used for the diagnosis of insulin resistance. We found that contrary to short-chain and medium-chain acylcarnitines, the measurements of changes in plasma long-chain acylcarnitine concentrations after glucose load in fasted subjects are useful as diagnostic markers for heart and muscle-specific insulin resistance in clinics.
Original languageEnglish
Pages165
Publication statusPublished - 24 Mar 2021
EventRSU Research week 2021: Knowledge for Use in Practice - Rīga, Latvia
Duration: 24 Mar 202126 Mar 2021
https://rw2021.rsu.lv/conferences/knowledge-use-practice

Conference

ConferenceRSU Research week 2021: Knowledge for Use in Practice
Abbreviated titleRW2021
CountryLatvia
CityRīga
Period24/03/2126/03/21
Internet address

Field of Science

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type

  • 3.4. Other publications in conference proceedings (including local)

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