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Although NAD\n                    <jats:sup>+<\/jats:sup>\n                    also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from\n                    <jats:italic>Lactobacillus brevis<\/jats:italic>\n                    (\n                    <jats:italic>Lb<\/jats:italic>\n                    NOX) increases daytime body temperature and blood and liver acyl-carnitines.\n                    <jats:italic>Lb<\/jats:italic>\n                    NOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPAR\u03b1) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably,\n                    <jats:italic>Sirt1<\/jats:italic>\n                    liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by\n                    <jats:italic>Lb<\/jats:italic>\n                    NOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.\n                  <\/jats:p>","DOI":"10.1038\/s42255-021-00498-1","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T12:47:34Z","timestamp":1639399654000},"page":"1621-1632","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3453-951X","authenticated-orcid":false,"given":"Daniel C.","family":"Levine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yu","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Kyung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-8372","authenticated-orcid":false,"given":"Jonathan","family":"Cedernaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9938-382X","authenticated-orcid":false,"given":"Chelsea","family":"Hepler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1981-0180","authenticated-orcid":false,"given":"Alexandra G.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith A.","family":"Sommars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biliana","family":"Marcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-6064","authenticated-orcid":false,"given":"Peng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-0883","authenticated-orcid":false,"given":"Olga R.","family":"Ilkayeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-4290","authenticated-orcid":false,"given":"Chiaki","family":"Omura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-7835","authenticated-orcid":false,"given":"Kathryn M.","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-691X","authenticated-orcid":false,"given":"Christopher B.","family":"Newgard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-0546","authenticated-orcid":false,"given":"Grant D.","family":"Barish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Bien","family":"Peek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-3886","authenticated-orcid":false,"given":"Navdeep S.","family":"Chandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4964-796X","authenticated-orcid":false,"given":"Milan","family":"Mrksich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1602-8601","authenticated-orcid":false,"given":"Joseph","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"498_CR1","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1126\/science.aah4965","volume":"354","author":"J Bass","year":"2016","unstructured":"Bass, J. & Lazar, M. 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