{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:32:46Z","timestamp":1790703166525,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver\/hepatocyte-derived FGF21.<\/jats:p>","DOI":"10.3390\/nu13051469","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T06:19:11Z","timestamp":1619504351000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dietary Essential Amino Acid Restriction Promotes Hyperdipsia via Hepatic FGF21"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-1976","authenticated-orcid":false,"given":"Patricia M.","family":"Rusu","sequence":"first","affiliation":[{"name":"Nutrient Metabolism &amp; Signalling Laboratory, Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, 3800 Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Nutrient Metabolism &amp; Signalling Laboratory, Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, 3800 Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Heikenwalder","sequence":"additional","affiliation":[{"name":"Division Chronic Inflammation and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8223-2638","authenticated-orcid":false,"given":"Oliver J.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Kiel and DZHK (German Centre for Cardiovascular Research), 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9132-8244","authenticated-orcid":false,"given":"Adam J.","family":"Rose","sequence":"additional","affiliation":[{"name":"Nutrient Metabolism &amp; Signalling Laboratory, Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, 3800 Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.2105\/AJPH.58.11.2020","article-title":"The sequence of events leading to the establishment of the amino acid needs of man","volume":"58","author":"Rose","year":"1968","journal-title":"Am. 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