Extensive profiling of histidine-containing dipeptides reveals species- and tissue-specific distribution and metabolism in mice, rats, and humans

Thibaux Van der Stede, Jan Spaas, Sarah de Jager, Jana De Brandt, Camilla Hansen, Jan Stautemas, Bjarne Vercammen, Siegrid De Baere, Siska Croubels, Charles-Henri Van Assche, Berta Cillero Pastor, Michiel Vandenbosch, Ruud Van Thienen, Kenneth Verboven, Dominique Hansen, Thierry Bové, Bruno Lapauw, Charles Van Praet, Karel Decaestecker, Bart VanaudenaerdeBert O. Eijnde, Lasse Gliemann, Ylva Hellsten, Wim Derave*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

7 Citations (Scopus)

Abstract

Aim: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear.

Methods: Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively).

Results: Our data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion.

Conclusion: Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease.

Original languageEnglish
Article numbere14020
JournalActa Physiologica
Volume239
Issue number1
Number of pages21
ISSN1748-1708
DOIs
Publication statusPublished - 2023

Bibliographical note

© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Keywords

  • Faculty of Science
  • Carnosine
  • Central nervous system
  • Exercise
  • Histidine-containing dipeptides
  • Muscle

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