{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:11:30Z","timestamp":1792271490917,"version":"4.4.0"},"reference-count":18,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a Grant in-Aid for Scientific Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tryptophan hydroxylase (Tph), the rate-limiting enzyme of serotonin (5-hydroxytryptophan; 5-HT) synthesis, exists in two isoforms, Tph1 and Tph2. Tph1 upregulates peripheral 5-HT synthesis and blood 5-HT levels, whereas Tph2 upregulates brain 5-HT synthesis. Here, we show that plasma and brain levels of tryptophan and its metabolites, including 5-HT, 5-hydroxy indoleacetic acid, indolepropionic acid, indole-3-acetic acid, kynurenine, and xanthurenic acid, are decreased in young (8-week-old) Tph1-mutant mice compared with age-matched wild-type mice. In older (7-month-old) Tph1-mutants, the decreases in tryptophan and its metabolites outside the 5-HT pathway were diminished. Although single-housed Tph1 mutants displayed age-related alterations in food intake, body weight, and plasma FGF21 levels, blood glucose levels were lower in both young and older Tph1 mutants compared with age-matched wild-type mice. These findings suggest that Tph1 regulates tryptophan and its metabolites in the plasma and brain, as well as blood glucose homeostasis.<\/jats:p>","DOI":"10.3390\/ijms26093978","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"3978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tryptophan Hydroxylase 1 Regulates Tryptophan and Its Metabolites"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6628-6246","authenticated-orcid":false,"given":"Katsunori","family":"Nonogaki","sequence":"first","affiliation":[{"name":"Division of Diabetes and Nutrition, RARiS, Tohoku University, 6-6-11 Aramakiaza-Aoba, Aoba-ku, Sendai 980-8579, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Kaji","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Nutrition, RARiS, Tohoku University, 6-6-11 Aramakiaza-Aoba, Aoba-ku, Sendai 980-8579, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1126\/science.1078197","article-title":"Synthesis of serotonin by a second tryptophan hydroxylase isoform","volume":"299","author":"Walther","year":"2003","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.euroneuro.2008.12.005","article-title":"Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: Convergent data from Tph2 knockout mice","volume":"19","author":"Gutknecht","year":"2009","journal-title":"Eur. 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