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Therefore, this study examined the impact of HT at 121\u2009\u00b0C on soy protein isolate (SPI) in water. After 20\u2009min of HT treatment, most amino acid levels in SPI decreased significantly, despite minimal nitrogen loss. HT also increased insoluble protein and larger soluble peptides after in vitro digestion. Mice administered HT-treated SPI showed lower serum levels of free amino acids, thereby reducing bioavailability. Long-term feeding with a 20% protein diet based on HT-treated SPI impaired social novelty recognition and decreased peripheral serotonin levels, while anxiety-like behavior, object close-range exploration, sociability, and serum tryptophan (Trp) remained unaffected. These findings indicate that HT treatment not only reduces the nutritional value of SPI but may also generate Maillard-type compounds or modified peptides that interfere with Trp metabolism and social behavior.<\/jats:p>","DOI":"10.1038\/s41538-026-01091-0","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:21:41Z","timestamp":1788409301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-temperature-treated soy protein isolate reduces amino acid availability and alters social novelty in mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Tomoko T.","family":"Asai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayo","family":"Mannari-Sasagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Yabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Horii-Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"1091_CR1","doi-asserted-by":"crossref","unstructured":"Holdsworth, S. 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