{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:22Z","timestamp":1787029222211,"version":"build-2736575974"},"reference-count":194,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["34561"],"award-info":[{"award-number":["34561"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]},{"award":["34561"],"award-info":[{"award-number":["34561"]}],"id":[{"id":"https:\/\/ror.org\/01n3s4692","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer\u2019s disease dementia. This taste boosts the immune system and induces saliva secretion. However, the molecular mechanisms linking umami peptides to systemic physiology remain poorly understood. This study provides the first integrated analysis of neurological, immunological, and endocrinological pathways activated by umami peptides. Methods: Novel umami peptides were identified using machine-learning and deep-learning analyses from a library of marine-derived bioactive peptides. T1R1-T1R3 heterodimer is the dominant receptor for umami taste transmission in humans, expressed on taste cells, intestinal cells, and hypothalamic tanycytes. Molecular docking confirmed the binding of novel ligands to the T1R1-T1R3 receptor complex. New candidates and experimentally validated umami peptides, identified by sensomics approaches from tauco, chicken soup, pufferfish, and dry-cured ham, were analyzed using gene ontology. Results: The functional enrichment analysis revealed crosstalk among key signaling processes, including glutamatergic and opioidergic pathways. In addition to the role of \u00b51 opioid receptor (OPRM1), hub gene intersections highlight cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and the anorexigenic pro-opiomelanocortin (POMC) neurons as potential regulators of the gut\u2013brain axis in satiety signaling. Chemokine-encoding genes, melanin-concentrating hormone (MCH), oxytocin (OXT), and neurotensin (NTS) were other key target genes. Conclusions: The identified targets reveal the coordinated crosstalk between peripheral and central umami signaling that may contribute to the regulation of feeding behavior, satiety, cognition, memory, learning, and immune function. These network-based insights generate hypotheses and guide the design of nutritional and drug-like effectors for metabolic and cognitive health.<\/jats:p>","DOI":"10.3390\/nu18081299","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:22:47Z","timestamp":1776691367000},"page":"1299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The NeuroImmunoEndocrine Circuit of Umami Peptides: A Systems Biology Approach"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-9569","authenticated-orcid":false,"given":"Shiva","family":"Hemmati","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran"},{"name":"Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran"},{"name":"Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolali","family":"Mohagheghzadeh","sequence":"additional","affiliation":[{"name":"Department of Phytopharmaceuticals, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71345-1583, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41581-021-00533-0","article-title":"The Impact of Excessive Salt Intake on Human Health","volume":"18","author":"Hunter","year":"2022","journal-title":"Nat. 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