Extensive profiling of histidine-containing dipeptides reveals species-specific distribution and metabolism in mice, rats and humans
Publikation: Working paper › Preprint › Forskning
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Extensive profiling of histidine-containing dipeptides reveals species-specific distribution and metabolism in mice, rats and humans. / Stede, Thibaux Van der; Spaas, Jan; Jager, Sarah de; Brandt, Jana De; Hansen, Camilla; Vercammen, Bjarne; Baere, Siegrid De; Croubels, Siska; Thienen, Ruud Van; Verboven, Kenneth; Hansen, Dominique; Bové, Thierry; Lapauw, Bruno; Praet, Charles Van; Decaestecker, Karel; Vanaudenaerde, Bart; Eijnde, Bert O.; Gliemann, Lasse; Hellsten, Ylva; Derave, Wim.
bioRxiv, 2023. s. 1-31.Publikation: Working paper › Preprint › Forskning
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T1 - Extensive profiling of histidine-containing dipeptides reveals species-specific distribution and metabolism in mice, rats and humans
AU - Stede, Thibaux Van der
AU - Spaas, Jan
AU - Jager, Sarah de
AU - Brandt, Jana De
AU - Hansen, Camilla
AU - Vercammen, Bjarne
AU - Baere, Siegrid De
AU - Croubels, Siska
AU - Thienen, Ruud Van
AU - Verboven, Kenneth
AU - Hansen, Dominique
AU - Bové, Thierry
AU - Lapauw, Bruno
AU - Praet, Charles Van
AU - Decaestecker, Karel
AU - Vanaudenaerde, Bart
AU - Eijnde, Bert O.
AU - Gliemann, Lasse
AU - Hellsten, Ylva
AU - Derave, Wim
N1 - (Preprint)
PY - 2023/2/19
Y1 - 2023/2/19
N2 - 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.
AB - 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.
U2 - 10.1101/2023.02.16.528841
DO - 10.1101/2023.02.16.528841
M3 - Preprint
SP - 1
EP - 31
BT - Extensive profiling of histidine-containing dipeptides reveals species-specific distribution and metabolism in mice, rats and humans
PB - bioRxiv
ER -
ID: 336748875