{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:26:16Z","timestamp":1789007176435,"version":"build-2803163510"},"reference-count":37,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sodium valporate (VPA), a broad-spectrum inhibitor of histone deacetylases (HDACs), increased ghrelin whereas decreased nesfatin-1 in mice fed normal chow diet or high-fat diet. Alterations in ghrelin and nucleobindin 2\/nesfatin-1 were mediated by HDAC5 but not HDAC4. Activation of mTORC1 significantly attenuated the effect of VPA on ghrelin and nesfatin-1 levels. HDAC5 coimmunoprecipitated with raptor. Inhibition of HDAC5 by VPA, trichostatin A, or siHDAC5 markedly increased acetylation of raptor Lys840 and subsequent phosphorylation of raptor Ser792, resulting in suppression of mTORC1 signaling. A raptor mutant lacking the Lys840 acetylation site showed a decrement in phosphorylation of raptor Ser792 and subsequent increase in mTORC1 signaling. These alterations were associated with reciprocal changes in ghrelin and nucleobindin 2\/nesfatin-1 expression. These findings reveal HDAC5-mTORC1 signaling as a novel mechanism in the differential regulation of gastric ghrelin and nesfatin-1.<\/jats:p>","DOI":"10.1210\/me.2015-1184","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T01:03:41Z","timestamp":1441933421000},"page":"1571-1580","source":"Crossref","is-referenced-by-count":18,"title":["HDAC5-mTORC1 Interaction in Differential Regulation of Ghrelin and Nucleobindin 2 (NUCB2)\/Nesfatin-1"],"prefix":"10.1210","volume":"29","author":[{"given":"Liangxiao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Mulholland","sequence":"first","affiliation":[{"name":"Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology (L.M., H.T., Y.Y., R.Y., J.Z., Y.L., W.Z.), Peking University Health Science Center, Beijing 100191, China"},{"name":"Department of Surgery (M.M., W.Z.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0346"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613000351300_B1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"2020071613000351300_B2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1053\/gast.2001.22158","article-title":"Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin","volume":"120","author":"Asakawa","year":"2001","journal-title":"Gastroenterology"},{"key":"2020071613000351300_B3","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.2337\/diabetes.50.11.2438","article-title":"Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats","volume":"50","author":"Kamegai","year":"2001","journal-title":"Diabetes"},{"key":"2020071613000351300_B4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cmet.2006.09.004","article-title":"Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus","volume":"4","author":"Date","year":"2006","journal-title":"Cell Metab"},{"key":"2020071613000351300_B5","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.2337\/db12-1451","article-title":"Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin","volume":"62","author":"Ram\u00edrez","year":"2013","journal-title":"Diabetes"},{"key":"2020071613000351300_B6","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nature05162","article-title":"Identification of nesfatin-1 as a satiety molecule in the hypothalamus","volume":"443","author":"Oh","year":"2006","journal-title":"Nature"},{"key":"2020071613000351300_B7","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1210\/en.2008-0747","article-title":"Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa","volume":"150","author":"Stengel","year":"2009","journal-title":"Endocrinology"},{"key":"2020071613000351300_B8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2337\/db05-0996","article-title":"Exendin-4 potently decreases ghrelin levels in fasting rats","volume":"56","author":"P\u00e9rez-Tilve","year":"2007","journal-title":"Diabetes"},{"key":"2020071613000351300_B9","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1210\/en.2009-0372","article-title":"Gastric mammalian target of rapamycin signaling regulates ghrelin production and food intake","volume":"150","author":"Xu","year":"2009","journal-title":"Endocrinology"},{"key":"2020071613000351300_B10","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.2174\/138161281939131127143306","article-title":"Regulation of gastric nesfatin-1\/NUCB2","volume":"19","author":"Li","year":"2013","journal-title":"Curr Pharm Des"},{"key":"2020071613000351300_B11","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1159\/000338503","article-title":"mTOR-dependent modulation of gastric nesfatin-1\/NUCB2","volume":"29","author":"Li","year":"2012","journal-title":"Cell Physiol Biochem"},{"key":"2020071613000351300_B12","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1212\/01.wnl.0000187074.27586.d1","article-title":"Leptin, ghrelin, and adiponectin in epileptic patients treated with valproic acid","volume":"65","author":"Greco","year":"2005","journal-title":"Neurology"},{"key":"2020071613000351300_B13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1074\/jbc.M111.304337","article-title":"Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein","volume":"287","author":"Glidden","year":"2012","journal-title":"J Biol Chem"},{"key":"2020071613000351300_B14","doi-asserted-by":"crossref","first-page":"13132","DOI":"10.1074\/jbc.M113.520734","article-title":"Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation","volume":"289","author":"Hong","year":"2014","journal-title":"J Biol Chem"},{"key":"2020071613000351300_B15","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/j.0013-9580.2004.00104.x","article-title":"The activity of antiepileptic drugs as histone deacetylase inhibitors","volume":"45","author":"Eyal","year":"2004","journal-title":"Epilepsia"},{"key":"2020071613000351300_B16","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0304-3940(02)01381-2","article-title":"Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus","volume":"341","author":"Riediger","year":"2003","journal-title":"Neurosci Lett"},{"key":"2020071613000351300_B17","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1073\/pnas.0500619102","article-title":"Effect of centrally administered C75, a fatty acid synthase inhibitor, on ghrelin secretion and its downstream effects","volume":"102","author":"Hu","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613000351300_B18","doi-asserted-by":"crossref","first-page":"860","DOI":"10.2337\/db07-0843","article-title":"AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5","volume":"57","author":"McGee","year":"2008","journal-title":"Diabetes"},{"key":"2020071613000351300_B19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1530\/JME-12-0095","article-title":"Histone deacetylase 5 regulates glucose uptake and insulin action in muscle cells","volume":"49","author":"Raichur","year":"2012","journal-title":"J Mol Endocrinol"},{"key":"2020071613000351300_B20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nature07349","article-title":"A fasting inducible switch modulates gluconeogenesis via activator\/coactivator exchange","volume":"456","author":"Liu","year":"2008","journal-title":"Nature"},{"key":"2020071613000351300_B21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1677\/JOE-09-0345","article-title":"Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5","volume":"205","author":"Caton","year":"2010","journal-title":"J Endocrinol"},{"key":"2020071613000351300_B22","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1371\/journal.pbio.0040031","article-title":"Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic \u03b2 cells","volume":"4","author":"Bordone","year":"2006","journal-title":"PLoS Biol"},{"key":"2020071613000351300_B23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature05354","article-title":"Resveratrol improves health and survival of mice on a high-calorie diet","volume":"444","author":"Baur","year":"2006","journal-title":"Nature"},{"key":"2020071613000351300_B24","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cell.2006.11.013","article-title":"Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1\u03b1","volume":"127","author":"Lagouge","year":"2006","journal-title":"Cell"},{"key":"2020071613000351300_B25","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nature06261","article-title":"Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes","volume":"450","author":"Milne","year":"2007","journal-title":"Nature"},{"key":"2020071613000351300_B26","doi-asserted-by":"crossref","first-page":"9793","DOI":"10.1073\/pnas.0802917105","article-title":"Sirt1 protects against high-fat diet-induced metabolic damage","volume":"105","author":"Pfluger","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613000351300_B27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmet.2008.08.014","article-title":"SirT1 gain of function increases energy efficiency and prevents diabetes in mice","volume":"8","author":"Banks","year":"2008","journal-title":"Cell Metab"},{"key":"2020071613000351300_B28","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1074\/jbc.M110.176842","article-title":"Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E \u03b2-cells and human islets through a SIRT1-dependent mechanism","volume":"286","author":"Vetterli","year":"2011","journal-title":"J Biol Chem"},{"key":"2020071613000351300_B29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.cmet.2009.02.006","article-title":"Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation","volume":"9","author":"Purushotham","year":"2009","journal-title":"Cell Metab"},{"key":"2020071613000351300_B30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1053\/j.gastro.2013.10.059","article-title":"Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21","volume":"146","author":"Li","year":"2014","journal-title":"Gastroenterology"},{"key":"2020071613000351300_B31","doi-asserted-by":"crossref","first-page":"e71513","DOI":"10.1371\/journal.pone.0071513","article-title":"Peripheral effects of nesfatin-1 on glucose homeostasis","volume":"8","author":"Li","year":"2013","journal-title":"PLoS One"},{"key":"2020071613000351300_B32","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1210\/en.2009-0578","article-title":"Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor","volume":"150","author":"Stengel","year":"2009","journal-title":"Endocrinology"},{"key":"2020071613000351300_B33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.peptides.2010.09.027","article-title":"Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals","volume":"32","author":"Goebel","year":"2011","journal-title":"Peptides"},{"key":"2020071613000351300_B34","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/454287a","article-title":"Signal transduction: linking nutrients to growth","volume":"454","author":"Zinzalla","year":"2008","journal-title":"Nature"},{"key":"2020071613000351300_B35","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"2020071613000351300_B36","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(02)00833-4","article-title":"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action","volume":"110","author":"Hara","year":"2002","journal-title":"Cell"},{"key":"2020071613000351300_B37","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol Cell"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/29\/11\/1571\/8909388\/mend1571.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/29\/11\/1571\/8909388\/mend1571.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T22:41:42Z","timestamp":1594939302000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/29\/11\/1571\/2556359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,1]]},"references-count":37,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2015-1184","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,1]]}}}