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

Thibaux Van der Stede, Jan Spaas, Sarah de Jager, Jana De Brandt, Camilla Hansen, Bjarne Vercammen, Siegrid De Baere, Siska Croubels, Ruud Van Thienen, Kenneth Verboven, Dominique Hansen, Thierry Bové, Bruno Lapauw, Charles Van Praet, Karel Decaestecker, Bart Vanaudenaerde, Bert O. Eijnde, Lasse Gliemann, Ylva Hellsten, Wim Derave*

*Corresponding author af dette arbejde

Publikation: Working paperPreprintForskning

Abstract

Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules linked to inflammatory, metabolic and neurological diseases, as well as exercise performance. 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, n=19 tissues, respectively). Our data show that tissue HCD levels are uniquely regulated by carnosine synthase, an enzyme preferentially expressed by fast-twitch skeletal muscle fibers and brain oligodendrocytes. Cardiac HCD levels are remarkably low. The low abundant HCD N-acetylcarnosine is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation as the most stable plasma HCD, which is further induced by acute exercise in a myokine-like fashion. Carnosine is preferentially transported within red blood cells in humans but not rodents. We provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease.
OriginalsprogEngelsk
UdgiverbioRxiv
Sider1-31
Antal sider31
DOI
StatusUdgivet - 19 feb. 2023

Bibliografisk note

(Preprint)

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