{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:55:41Z","timestamp":1791492941922,"version":"4.3.4"},"reference-count":37,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leptin production by adipose cells in vivo is increased after feeding and decreased by food deprivation. However, molecular mechanisms that control leptin expression in response to food intake remain unknown. Here, we test the hypothesis that leptin expression in adipose cells is regulated by nutrient- and insulin-sensitive mammalian target of rapamycin complex 1 (mTORC1)-mediated pathway. The activity of mTORC1 in 3T3-L1 adipocytes was up-regulated by stable expression of either constitutively active Rheb or dominant-negative AMP-activated protein kinase. In both cases, expression of endogenous leptin was significantly elevated at the level of translation. To investigate the role of leptin 5\u2032-untranslated region (UTR) in the regulation of protein expression, we created bicistronic reporter constructs with and without the 5\u2032-UTR. We found that the presence of leptin 5\u2032-UTR renders mRNA resistant to regulation by mTORC1. It appears, therefore, that mTORC1 controls translation of leptin mRNA via a novel mechanism that does not require the presence of either the 5\u2032-terminal oligopyrimidine tract or the 5\u2032-UTR.<\/jats:p>","DOI":"10.1210\/me.2008-0148","type":"journal-article","created":{"date-parts":[[2008,7,25]],"date-time":"2008-07-25T01:49:03Z","timestamp":1216950543000},"page":"2260-2267","source":"Crossref","is-referenced-by-count":20,"title":["The Mammalian Target of Rapamycin Complex 1 Regulates Leptin Biosynthesis in Adipocytes at the Level of Translation: The Role of the 5\u2032-Untranslated Region in the Expression of Leptin Messenger Ribonucleic Acid"],"prefix":"10.1210","volume":"22","author":[{"given":"Partha","family":"Chakrabarti","sequence":"first","affiliation":[{"name":"Boston University School of Medicine (P.C., T.A., Z.L., K.V.K.), Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Anno","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine (P.C., T.A., Z.L., K.V.K.), Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan D.","family":"Manning","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health (B.D.M.), Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Luo","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine (P.C., T.A., Z.L., K.V.K.), Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin V.","family":"Kandror","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine (P.C., T.A., Z.L., K.V.K.), Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614141347300_R1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev.physiol.62.1.413","article-title":"Leptin.","volume":"62","author":"Ahima","year":"2000","journal-title":"Annu Rev Physiol"},{"key":"2020071614141347300_R2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1006\/bbrc.1997.7086","article-title":"Effect of enteral versus parenteral nutrition on leptin gene expression and release into the circulation.","volume":"237","author":"Levy","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614141347300_R3","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1172\/JCI118206","article-title":"Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity.","volume":"96","author":"Frederich","year":"1995","journal-title":"J Clin Invest"},{"key":"2020071614141347300_R4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/0014-5793(95)00943-4","article-title":"Diet- and diabetes-induced changes of ob gene expression in rat adipose tissue.","volume":"371","author":"Becker","year":"1995","journal-title":"FEBS Lett"},{"key":"2020071614141347300_R5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/377527a0","article-title":"Transient increase in obese gene expression after food intake or insulin administration.","volume":"377","author":"Saladin","year":"1995","journal-title":"Nature"},{"key":"2020071614141347300_R6","doi-asserted-by":"crossref","first-page":"9034","DOI":"10.1073\/pnas.92.20.9034","article-title":"Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes.","volume":"92","author":"MacDougald","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614141347300_R7","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1194\/jlr.M600065-JLR200","article-title":"Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue.","volume":"47","author":"Lee","year":"2006","journal-title":"J Lipid Res"},{"key":"2020071614141347300_R8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1074\/jbc.M609518200","article-title":"Feeding and insulin increase leptin translation. Importance of the leptin mRNA untranslated regions.","volume":"282","author":"Lee","year":"2007","journal-title":"J Biol Chem"},{"key":"2020071614141347300_R9","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1210\/endo.138.10.5451","article-title":"Insulin stimulates both leptin secretion and production by rat white adipose tissue.","volume":"138","author":"Barr","year":"1997","journal-title":"Endocrinology"},{"key":"2020071614141347300_R10","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1210\/endo.142.8.8313","article-title":"The effects of insulin, glucose, and pyruvate on the kinetics of leptin secretion.","volume":"142","author":"Levy","year":"2001","journal-title":"Endocrinology"},{"key":"2020071614141347300_R11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1210\/endo.139.2.5716","article-title":"Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.","volume":"139","author":"Mueller","year":"1998","journal-title":"Endocrinology"},{"key":"2020071614141347300_R12","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2337\/diabetes.48.2.272","article-title":"Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes.","volume":"48","author":"Bradley","year":"1999","journal-title":"Diabetes"},{"key":"2020071614141347300_R13"},{"key":"2020071614141347300_R14"},{"key":"2020071614141347300_R15","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":"2020071614141347300_R16","doi-asserted-by":"crossref","first-page":"9583","DOI":"10.1074\/jbc.R000034200","article-title":"The TOR kinases link nutrient sensing to cell growth.","volume":"276","author":"Rohde","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071614141347300_R17","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbrc.2003.07.019","article-title":"mTOR integrates amino acid- and energy-sensing pathways.","volume":"313","author":"Tokunaga","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614141347300_R18"},{"key":"2020071614141347300_R19","doi-asserted-by":"crossref","first-page":"19793","DOI":"10.1074\/jbc.C600028200","article-title":"Hyperactivation of mammalian target of rapamycin (mTOR) signaling by a gain-of-function mutant of the Rheb GTPase.","volume":"281","author":"Yan","year":"2006","journal-title":"J Biol Chem"},{"key":"2020071614141347300_R20","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.tibs.2003.09.003","article-title":"Rheb fills a GAP between TSC and TOR.","volume":"28","author":"Manning","year":"2003","journal-title":"Trends Biochem Sci"},{"key":"2020071614141347300_R21","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1101\/gad.887201","article-title":"Regulation of translation initiation by FRAP\/mTOR.","volume":"15","author":"Gingras","year":"2001","journal-title":"Genes Dev"},{"key":"2020071614141347300_R22","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1128\/MCB.20.18.6704-6711.2000","article-title":"Characterization of the role of AMP-activated protein kinase in the regulation of glucose-activated gene expression using constitutively active and dominant negative forms of the kinase.","volume":"20","author":"Woods","year":"2000","journal-title":"Mol Cell Biol"},{"key":"2020071614141347300_R23","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival.","volume":"115","author":"Inoki","year":"2003","journal-title":"Cell"},{"key":"2020071614141347300_R24","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"},{"key":"2020071614141347300_R25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tibs.2003.11.007","article-title":"TSC2: filling the GAP in the mTOR signaling pathway.","volume":"29","author":"Li","year":"2004","journal-title":"Trends Biochem Sci"},{"key":"2020071614141347300_R26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1126\/science.7939721","article-title":"PHAS-I as a link between mitogen-activated protein kinase and translation initiation.","volume":"266","author":"Lin","year":"1994","journal-title":"Science"},{"key":"2020071614141347300_R27","doi-asserted-by":"crossref","first-page":"18531","DOI":"10.1074\/jbc.270.31.18531","article-title":"Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase-independent pathway.","volume":"270","author":"Lin","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614141347300_R28","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1210\/endo.138.8.5263","article-title":"A constitutively active version of the Ser\/Thr kinase Akt induces production of the ob gene product, leptin, in 3T3-L1 adipocytes.","volume":"138","author":"Barthel","year":"1997","journal-title":"Endocrinology"},{"key":"2020071614141347300_R29"},{"key":"2020071614141347300_R30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0092-8674(00)00117-3","article-title":"TOR, a central controller of cell growth.","volume":"103","author":"Schmelzle","year":"2000","journal-title":"Cell"},{"key":"2020071614141347300_R31"},{"key":"2020071614141347300_R32","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nm0597-575","article-title":"Human leptin levels are pulsatile and inversely related to pituitary-adrenal function.","volume":"3","author":"Licinio","year":"1997","journal-title":"Nat Med"},{"key":"2020071614141347300_R33","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1073\/pnas.95.5.2541","article-title":"Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women.","volume":"95","author":"Licinio","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614141347300_R34","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1006\/bbrc.1996.1724","article-title":"Ultradian oscillations of leptin secretion in humans.","volume":"228","author":"Sinha","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614141347300_R35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/mthe.2000.0095","article-title":"Development of a novel trans-lentiviral vector that affords predictable safety.","volume":"2","author":"Wu","year":"2000","journal-title":"Mol Ther"},{"key":"2020071614141347300_R36","doi-asserted-by":"crossref","first-page":"47972","DOI":"10.1074\/jbc.C200486200","article-title":"Translocation of small preformed vesicles is responsible for the insulin activation of glucose transport in adipose cells. Evidence from the in vitro reconstitution assay.","volume":"277","author":"Xu","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071614141347300_R37"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/22\/10\/2260\/8937126\/mend2260.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/22\/10\/2260\/8937126\/mend2260.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T01:43:19Z","timestamp":1594950199000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/22\/10\/2260\/2737936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,1]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2008-0148","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,1]]}}}