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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Jan Spaas
  • Sarah de Jager
  • Jana De Brandt
  • 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 Vanaudenaerde
  • Bert O. Eijnde
  • Wim Derave

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.

TidsskriftActa Physiologica
Udgave nummer1
Antal sider21
StatusUdgivet - 2023

Bibliografisk note

CURIS 2023 NEXS 157

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

ID: 360692368