Dambrova 2018 MiP2018

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L-Carnitine: from discovery to cardiometabolic risk markers.

Link: MiP2018

Dambrova M, Liepinsh E (2018)

Event: MiP2018

COST Action MitoEAGLE

L-Carnitine was discovered more than hundred years ago by the Latvian biochemist R. Krimberg [1], but it took more than half a century until its role in long-chain fatty acid oxidation by mitochondria was described. In the 1970-80s, the cases of inborn errors in carnitine metabolism were reported and details of the enzymes and transporters of the carnitine system delineated at the genetic level. Nowadays L-carnitine is a very popular food supplement due to its safety profile and suggested effects on energy metabolism pathways [2]. L-carnitine is frequently used in cocktails of food supplements that are believed to increase fatty acid metabolism, eliminate body fat and increase fitness. However, the scientific evidence supporting its efficacy is inconclusive and the body weight-reducing effect of L-carnitine supplementation has not been proven clinically. In addition, L-carnitine is not considered as a doping agent, but it has been shown to positively impact the recovery process after exercise. To drive the processes of fatty acid metabolism, excessive concentrations of L-carnitine should reach the cellular mitochondria, but its bioavailability during normal homeostasis is quite low. The intake of high doses of L-carnitine impacts body levels of L-carnitine metabolites, long-chain acylcarnitines and trimethylamine-N-oxide. The increase in the tissue and plasma pools of long-chain acylcarnitines has been linked to the disturbed energy metabolism and development of insulin resistance, as well as increased ischemia-reperfusion damage [3]. Elevated trimethylamine-N-oxide levels impair pyruvate and fatty acid oxidation in cardiac mitochondria and predict an increased risk of cardiometabolic diseases and an increased incidence of major adverse cardiac events [4]. More studies are needed to evaluate the hypothesis of long-chain acylcarnitines and trimethylamine-N-oxide as novel diagnostic markers and to use L-carnitine-related pathway regulation to treat cardiovascular diseases and diabetes.


Bioblast editor: Plangger M, Kandolf G


Labels: MiParea: Exercise physiology;nutrition;life style 




Regulation: Amino acid 




Affiliations

Dambrova M(1,2), Liepinsh E(1)

  1. Latvian Inst Organic Synthesis
  2. Riga Stradins Univ; Riga, Latvia. - maija.dambrova@farm.osi.lv

References

  1. Gulewitsch W, Krimberg R (1905) Zur Kenntnis der Extraktivstoffe der Muskeln. II. Mitteilung: Über das Carnitin. Hoppe Seylers Z Physiol Chem 45:5.
  2. Dambrova M, Liepinsh E (2015) Risks and benefits of Carnitine supplementation in diabetes. Exp Clin Endocrinol Diabetes 123:95-100.
  3. Liepinsh E, Makrecka-Kuka M, Volska K, Kuka J, Makarova E, Antone U, Sevostjanovs E, Vilskersts R, Strods A, Tars K, Dambrova M (2016) Long-chain acylcarnitines determine ischaemia/reperfusion-induced damage in heart mitochondria. Biochem J. 473:1191-202.
  4. Makrecka-Kuka M, Volska K, Antone U, Vilskersts R, Grinberga S, Bandere D, Liepinsh E, Dambrova M (2017) Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria. Toxicol Lett. 267:32-38.