{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:29:37Z","timestamp":1790998177925,"version":"4.1.0"},"reference-count":127,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rev Endocr Metab Disord"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s11154-021-09636-2","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T05:02:36Z","timestamp":1617685356000},"page":"87-101","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Leptin, the brain and energy homeostasis: From an apparently simple to a highly complex neuronal system"],"prefix":"10.1007","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8534-2450","authenticated-orcid":false,"given":"Margherita","family":"Maffei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-5855","authenticated-orcid":false,"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"9636_CR1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1001\/jama.2009.2014","volume":"303","author":"KM Flegal","year":"2010","unstructured":"Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999\u20132008. JAMA. 2010;303:235\u201341.","journal-title":"JAMA"},{"key":"9636_CR2","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.appet.2008.06.009","volume":"51","author":"RE Keesey","year":"2008","unstructured":"Keesey RE, Powley TL. Body energy homeostasis. Appetite. 2008;51:442\u20135.","journal-title":"Appetite"},{"key":"9636_CR3","first-page":"535","volume":"137","author":"GC Kennedy","year":"1950","unstructured":"Kennedy GC. The hypothalamic control of food intake in rats. Proc R Soc L B Biol Sci. 1950;137:535\u201349.","journal-title":"Proc R Soc L B Biol Sci"},{"key":"9636_CR4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1959.sp006145","author":"GR Hervey","year":"1959","unstructured":"Hervey GR. The effects of lesions in the hypothalamus in parabiotic rats. J Physiol. 1959. https:\/\/doi.org\/10.1113\/jphysiol.1959.sp006145.","journal-title":"J Physiol"},{"key":"9636_CR5","first-page":"275","volume":"11","author":"RB Harris","year":"1987","unstructured":"Harris RB, Hervey E, Hervey GR, Tobin G. Body composition of lean and obese Zucker rats in parabiosis. Int J Obes. 1987;11:275\u201383.","journal-title":"Int J Obes"},{"key":"9636_CR6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/222629a0","volume":"222","author":"GR Hervey","year":"1969","unstructured":"Hervey GR. Regulation of energy balance. Nature. 1969;222:629\u201331.","journal-title":"Nature"},{"key":"9636_CR7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00429772","volume":"14","author":"DL Coleman","year":"1978","unstructured":"Coleman DL. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia. 1978;14:141\u20138.","journal-title":"Diabetologia"},{"key":"9636_CR8","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/nm1010-1097","volume":"16","author":"DL Coleman","year":"2010","unstructured":"Coleman DL. A historical perspective on leptin. Nat Med. 2010;16:1097\u20139.","journal-title":"Nat Med"},{"key":"9636_CR9","doi-asserted-by":"crossref","first-page":"8642","DOI":"10.1073\/pnas.87.21.8642","volume":"87","author":"N Bahary","year":"1990","unstructured":"Bahary N, Leibel RL, Joseph L, Friedman JM. Molecular mapping of the mouse db mutation. Proc Natl Acad Sci U S A. 1990;87:8642\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/0092-8674(86)90799-3","volume":"47","author":"SH Orkin","year":"1986","unstructured":"Orkin SH. Reverse genetics and human disease. Cell. 1986;47:845\u201350.","journal-title":"Cell"},{"key":"9636_CR11","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-09915-6_1","author":"M Maffei","year":"2015","unstructured":"Maffei M. Discovery of leptin and elucidation of leptin gene expression. Leptin Regul Clin Appl. 2015. https:\/\/doi.org\/10.1007\/978-3-319-09915-6_1.","journal-title":"Leptin Regul Clin Appl"},{"key":"9636_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0","author":"Y Zhang","year":"1994","unstructured":"Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994. https:\/\/doi.org\/10.1038\/372425a0.","journal-title":"Nature"},{"key":"9636_CR13","doi-asserted-by":"crossref","unstructured":"Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science (80- ).\u00a01995;269:543\u2013546.","DOI":"10.1126\/science.7624777"},{"key":"9636_CR14","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nm1195-1155","volume":"1","author":"M Maffei","year":"1995","unstructured":"Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1:1155\u201361.","journal-title":"Nat Med"},{"key":"9636_CR15","doi-asserted-by":"crossref","first-page":"6957","DOI":"10.1073\/pnas.92.15.6957","volume":"92","author":"M Maffei","year":"1995","unstructured":"Maffei M, Fei H, Lee GH, Dani C, Leroy P, Zhang Y, Proenca R, Negrel R, Ailhaud G, Friedman JM. Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci U S A. 1995;92:6957\u201360.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90151-5","volume-title":"Identification and expression cloning of a leptin receptor","author":"LA Tartaglia","year":"1995","unstructured":"Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor. OB-R: Cell; 1995. https:\/\/doi.org\/10.1016\/0092-8674(95)90151-5."},{"key":"9636_CR17","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/379632a0","volume":"379","author":"GH Lee","year":"1996","unstructured":"Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature. 1996;379:632\u20135.","journal-title":"Nature"},{"key":"9636_CR18","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1133","author":"K Takaya","year":"1996","unstructured":"Takaya K, Ogawa Y, Isse N, Okazaki T, Satoh N, Masuzaki H, Mori K, Tamura N, Hosoda K, Nakao K. Molecular cloning of rat leptin receptor isoform complementary DNAs-identification of a missense mutation in Zucker fatty (fa\/fa) rats. Biochem Biophys Res Commun. 1996. https:\/\/doi.org\/10.1006\/bbrc.1996.1133.","journal-title":"Biochem Biophys Res Commun"},{"key":"9636_CR19","doi-asserted-by":"publisher","DOI":"10.1530\/joe-14-0480","author":"IS Farooqi","year":"2014","unstructured":"Farooqi IS, O\u2019Rahilly S. 20 YEARS OF LEPTIN: Human disorders of leptin action. J Endocrinol. 2014. https:\/\/doi.org\/10.1530\/joe-14-0480.","journal-title":"J Endocrinol"},{"key":"9636_CR20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/me.2015-1232","volume":"30","author":"JN Flak","year":"2016","unstructured":"Flak JN, Myers MGJ. Minireview: CNS mechanisms of leptin actions. Mol Endocrinol. 2016;30:3\u201312.","journal-title":"Mol Endocrinol"},{"key":"9636_CR21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1006\/geno.1997.4962","volume":"45","author":"SCJ Chua","year":"1997","unstructured":"Chua SCJ, Koutras IK, Han L, Liu SM, Kay J, Young SJ, Chung WK, Leibel RL. Fine structure of the murine leptin receptor gene: splice site suppression is required to form two alternatively spliced transcripts. Genomics. 1997;45:264\u201370.","journal-title":"Genomics"},{"key":"9636_CR22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0092-8674(00)81294-5","volume":"84","author":"H Chen","year":"1996","unstructured":"Chen H, Charlat O, Tartaglia LA, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db\/db mice. Cell. 1996;84:491\u20135.","journal-title":"Cell"},{"key":"9636_CR23","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2337\/diabetes.50.2.425","volume":"50","author":"TJ Kowalski","year":"2001","unstructured":"Kowalski TJ, Liu SM, Leibel RL, Chua SCJ. Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity\/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes. 2001;50:425\u201335.","journal-title":"Diabetes"},{"key":"9636_CR24","first-page":"58","volume":"19","author":"EH Leiter","year":"1980","unstructured":"Leiter EH, Coleman DL, Eisenstein AB, Strack I. A new mutation (db3J) at the diabetes locus in strain 129\/J mice. I Physiological and histological characterization Diabetologia. 1980;19:58\u201365.","journal-title":"I Physiological and histological characterization Diabetologia"},{"key":"9636_CR25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199602013340503","volume":"334","author":"RV Considine","year":"1996","unstructured":"Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, TL B, . Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292\u20135.","journal-title":"N Engl J Med"},{"key":"9636_CR26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13041-020-00647-9","volume":"13","author":"Z Ren","year":"2020","unstructured":"Ren Z, Liu Y, Hong W, Pan X, Gong P, Liu Q, Zhou G, Qin S. Conditional knockout of leptin receptor in neural stem cells leads to obesity in mice and affects neuronal differentiation in the hypothalamus early after birth. Mol Brain. 2020;13:109.","journal-title":"Mol Brain"},{"key":"9636_CR27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0014-5793(96)00473-5","volume":"387","author":"JG Mercer","year":"1996","unstructured":"Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, Trayhurn P. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett. 1996;387:113\u20136.","journal-title":"FEBS Lett"},{"key":"9636_CR28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1172\/JCI118891","volume":"98","author":"MW Schwartz","year":"1996","unstructured":"Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG. Identification of targets of leptin action in rat hypothalamus. J Clin Invest. 1996;98:1101\u20136.","journal-title":"J Clin Invest"},{"key":"9636_CR29","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1073\/pnas.94.13.7001","volume":"94","author":"H Fei","year":"1997","unstructured":"Fei H, Okano HJ, Li C, Lee GH, Zhao C, Darnell R, Friedman JM. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci U S A. 1997;94:7001\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/(SICI)1096-9861(19980615)395:4<535::AID-CNE9>3.0.CO;2-2","volume":"395","author":"JK Elmquist","year":"1998","unstructured":"Elmquist JK, Bjorbaek C, Ahima RS, Flier JS, Saper CB. Distributions of leptin receptor mRNA isoforms in the rat brain. J Comp Neurol. 1998;395:535\u201347.","journal-title":"J Comp Neurol"},{"key":"9636_CR31","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainres.2008.03.078","volume":"1215","author":"A Frontini","year":"2008","unstructured":"Frontini A, Bertolotti P, Tonello C, Valerio A, Nisoli E, Cinti S, Giordano A. Leptin-dependent STAT3 phosphorylation in postnatal mouse hypothalamus. Brain Res. 2008;1215:105\u201315.","journal-title":"Brain Res"},{"key":"9636_CR32","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1172\/JCI41985","volume":"120","author":"LE Ring","year":"2010","unstructured":"Ring LE, Zeltser LM. Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels. J Clin Invest. 2010;120:2931\u201341.","journal-title":"J Clin Invest"},{"key":"9636_CR33","doi-asserted-by":"crossref","unstructured":"Villanueva EC, Mayers JMG (2008) Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes 32(Suppl.:S8\u2013S12","DOI":"10.1038\/ijo.2008.232"},{"key":"9636_CR34","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/nature01388","volume":"421","author":"SH Bates","year":"2003","unstructured":"Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, al. et, . STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421:856\u20139.","journal-title":"Nature"},{"key":"9636_CR35","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1210\/me.2007-0389","volume":"22","author":"ML Piper","year":"2008","unstructured":"Piper ML, Unger EK, Myers MGJ, Xu AW. Specific physiological roles for signal transducer and activator of transcription 3 in leptin receptor-expressing neurons. Mol Endocrinol. 2008;22:751\u20139.","journal-title":"Mol Endocrinol"},{"key":"9636_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077622","author":"S Ha","year":"2013","unstructured":"Ha S, Baver S, Huo L, et al. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. PLoS ONE. 2013. https:\/\/doi.org\/10.1371\/journal.pone.0077622.","journal-title":"PLoS ONE"},{"key":"9636_CR37","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/cne.22025","volume":"514","author":"MM Scott","year":"2009","unstructured":"Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF, Friedman JM, JK E, . Leptin targets in the mouse brain. J Comp Neurol. 2009;514:518\u201332.","journal-title":"J Comp Neurol"},{"key":"9636_CR38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cmet.2008.12.001","volume":"9","author":"MGJ Myers","year":"2009","unstructured":"Myers MGJ, M\u00fcnzberg H, Leinninger GM, Leshan RL. The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab. 2009;9:117\u201323.","journal-title":"Cell Metab"},{"key":"9636_CR39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.brainres.2011.01.010","volume":"1378","author":"CM Patterson","year":"2011","unstructured":"Patterson CM, Leshan RL, Jones JC, Myers MGJ. Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells. Brain Res. 2011;1378:18\u201328.","journal-title":"Brain Res"},{"key":"9636_CR40","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nn.2739","volume":"14","author":"Y Aponte","year":"2011","unstructured":"Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14:351\u20135.","journal-title":"Nat Neurosci"},{"key":"9636_CR41","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1172\/JCI46229","volume":"121","author":"MJ Krashes","year":"2011","unstructured":"Krashes MJ, Koda S, Ye C, Rogan SC, Maratos-Flier ADS, E ACC, Roth BL, Lowell BB, . Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011;121:1424\u20138.","journal-title":"J Clin Invest"},{"key":"9636_CR42","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1523\/JNEUROSCI.2742-12.2013","volume":"33","author":"C Zhan","year":"2013","unstructured":"Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, Wu P, Luo M. Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. J Neurosci. 2013;33:3624\u201332.","journal-title":"J Neurosci"},{"key":"9636_CR43","first-page":"480","volume":"5","author":"JD Kim","year":"2014","unstructured":"Kim JD, Leyva S, Diano S. Hormonal regulation of the hypothalamic melanocortin system. Front Physiol. 2014;5:480.","journal-title":"Front Physiol"},{"key":"9636_CR44","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.cmet.2015.09.026","volume":"22","author":"MJ Waterson","year":"2015","unstructured":"Waterson MJ, Horvath TL. Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding. Cell Metab. 2015;22:962\u201370.","journal-title":"Cell Metab"},{"key":"9636_CR45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cmet.2009.06.011","volume":"10","author":"GM Leinninger","year":"2009","unstructured":"Leinninger GM, Jo YH, Leshan RL, et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10:89\u201398.","journal-title":"Cell Metab"},{"key":"9636_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.06.016","author":"GM Leinninger","year":"2011","unstructured":"Leinninger GM, Opland DM, Jo YH, et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 2011. https:\/\/doi.org\/10.1016\/j.cmet.2011.06.016.","journal-title":"Cell Metab"},{"key":"9636_CR47","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.metabol.2014.08.004","volume":"64","author":"H-K Park","year":"2015","unstructured":"Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine functions and metabolism. Metab. 2015;64:24\u201334.","journal-title":"Metab"},{"key":"9636_CR48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2891-6-3","volume":"16","author":"S Mahabir","year":"2007","unstructured":"Mahabir S, Baer D, Johnson LL, Roth M, Campbell W, Clevidence B, Taylor PR. Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study. Nutr J. 2007;16:3.","journal-title":"Nutr J"},{"key":"9636_CR49","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/bjs.9780","volume":"102","author":"M Raffaelli","year":"2015","unstructured":"Raffaelli M, Iaconelli A, Nanni G, Guidone C, Callari C, Fernandez Real JM, Bellantone R, Mingrone G. Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels. Br J Surg. 2015;102:682\u201390.","journal-title":"Br J Surg"},{"key":"9636_CR50","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2310\/JIM.0b013e3181cf91ca","volume":"58","author":"J Smiechowska","year":"2010","unstructured":"Smiechowska J, Utech A, Taffet G, Hayes T, Marcelli M, Garcia JM. Adipokines in patients with cancer anorexia and cachexia. J Investig Med. 2010;58:554\u20139.","journal-title":"J Investig Med"},{"key":"9636_CR51","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/s42255-019-0095-y","volume":"1","author":"JM Friedman","year":"2019","unstructured":"Friedman JM. Leptin and the endocrine control of energy balance. Nat Metab. 2019;1:754\u201364.","journal-title":"Nat Metab"},{"key":"9636_CR52","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1210\/endo.137.7.8770941","volume":"137","author":"IA Barash","year":"1996","unstructured":"Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996;137:3144\u20137.","journal-title":"Endocrinology"},{"key":"9636_CR53","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/ng0396-318","volume":"12","author":"FF Chehab","year":"1996","unstructured":"Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinantleptin. Nat Genet. 1996;12:318\u201320.","journal-title":"Nat Genet"},{"key":"9636_CR54","first-page":"2751","volume":"84","author":"JA Levine","year":"1999","unstructured":"Levine JA, Eberhardt NL, Jensen MD. Leptin responses to overfeeding: relationship with body fat and nonexercise activity thermogenesis. J Clin Endocrinol Metab. 1999;84:2751\u20134.","journal-title":"J Clin Endocrinol Metab"},{"key":"9636_CR55","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/bph.12949","volume":"172","author":"H M\u00fcller-Fielitz","year":"2015","unstructured":"M\u00fcller-Fielitz H, Lau M, Gei\u00dfler C, Werner L, Winkler M, Raasch W. Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats. Br J Pharmacol. 2015;172:857\u201368.","journal-title":"Br J Pharmacol"},{"key":"9636_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-238","author":"E Ravussin","year":"1997","unstructured":"Ravussin E, Pratley RE, Maffei M, Wang H, Friedman JM, Bennett PH, Bogardus C. Relatively low plasma leptin concentrations precede weight gain in Pima Indians. Nat Med. 1997. https:\/\/doi.org\/10.1038\/nm0297-238.","journal-title":"Nat Med"},{"key":"9636_CR57","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199602013340503","volume":"334","author":"RV Considine","year":"1996","unstructured":"Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MROJP, Marco CC, McKee LJ, Bauer TL. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292\u20135.","journal-title":"N Engl J Med"},{"key":"9636_CR58","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41591-019-0370-1","volume":"25","author":"OS Dallner","year":"2019","unstructured":"Dallner OS, Marinis JM, Lu YH, et al. Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nat Med. 2019;25:507\u201316.","journal-title":"Nat Med"},{"key":"9636_CR59","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909163411204","author":"IS Farooqi","year":"1999","unstructured":"Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O\u2019Rahilly S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999. https:\/\/doi.org\/10.1056\/NEJM199909163411204.","journal-title":"N Engl J Med"},{"key":"9636_CR60","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-018-0887-z","author":"D Ara\u00fajo-Vilar","year":"2019","unstructured":"Ara\u00fajo-Vilar D, Santini F. Diagnosis and treatment of lipodystrophy: a step-by-step approach. J Endocrinol Invest. 2019. https:\/\/doi.org\/10.1007\/s40618-018-0887-z.","journal-title":"J Endocrinol Invest"},{"key":"9636_CR61","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11892-018-1100-7","volume":"18","author":"B Akinci","year":"2018","unstructured":"Akinci B, Meral R, Oral EA. Update on Therapeutic Options in Lipodystrophy. Curr Diab Rep. 2018;18:139.","journal-title":"Curr Diab Rep"},{"key":"9636_CR62","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95476","author":"RJ Brown","year":"2018","unstructured":"Brown RJ, Valencia A, Startzell M, et al. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy. J Clin Invest. 2018. https:\/\/doi.org\/10.1172\/JCI95476.","journal-title":"J Clin Invest"},{"key":"9636_CR63","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1568","author":"SB Heymsfield","year":"1999","unstructured":"Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: A randomized, controlled, dose-escalation trial. J Am Med Assoc. 1999. https:\/\/doi.org\/10.1001\/jama.282.16.1568.","journal-title":"J Am Med Assoc"},{"key":"9636_CR64","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1172\/JCI9842","volume":"105","author":"K El-Haschimi","year":"2000","unstructured":"El-Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest. 2000;105:1827\u201332.","journal-title":"J Clin Invest"},{"key":"9636_CR65","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.tips.2015.07.003","volume":"36","author":"ZY Zhang","year":"2015","unstructured":"Zhang ZY, Dodd GT, Tiganis T. Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling. Trends Pharmacol Sci. 2015;36:661\u201374.","journal-title":"Trends Pharmacol Sci"},{"key":"9636_CR66","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nm1072","volume":"10","author":"JK Howard","year":"2004","unstructured":"Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bj\u00f8rbaek C, Flier JS. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med. 2004;10:734\u20138.","journal-title":"Nat Med"},{"key":"9636_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2199","author":"D Ron","year":"2007","unstructured":"Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007. https:\/\/doi.org\/10.1038\/nrm2199.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"9636_CR68","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074134","author":"M Schr\u00f6der","year":"2005","unstructured":"Schr\u00f6der M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem. 2005. https:\/\/doi.org\/10.1146\/annurev.biochem.73.011303.074134.","journal-title":"Annu Rev Biochem"},{"key":"9636_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/nm1259","author":"D Scheuner","year":"2005","unstructured":"Scheuner D, Vander MD, Song B, Flamez D, Creemers JWM, Tsukamoto K, Ribick M, Schuit FC, Kaufman RJ. Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis. Nat Med. 2005. https:\/\/doi.org\/10.1038\/nm1259.","journal-title":"Nat Med"},{"key":"9636_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.07.009","author":"P Mardones","year":"2014","unstructured":"Mardones P, Dillin A, Hetz C. Cell-nonautonomous control of the UPR: Mastering energy homeostasis. Cell Metab. 2014. https:\/\/doi.org\/10.1016\/j.cmet.2014.07.009.","journal-title":"Cell Metab"},{"key":"9636_CR71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.06.002","author":"KW Williams","year":"2014","unstructured":"Williams KW, Liu T, Kong X, et al. Xbp1s in pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell Metab. 2014. https:\/\/doi.org\/10.1016\/j.cmet.2014.06.002.","journal-title":"Cell Metab"},{"key":"9636_CR72","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cmet.2008.12.004","volume":"9","author":"L Ozcan","year":"2009","unstructured":"Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, Myers MG Jr, Ozcan U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35\u201351.","journal-title":"Cell Metab"},{"key":"9636_CR73","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.11.051","author":"SW Ng","year":"2019","unstructured":"Ng SW, Chan Y, Chellappan DK, et al. Molecular modulators of celastrol as the keystones for its diverse pharmacological activities. Biomed Pharmacother. 2019. https:\/\/doi.org\/10.1016\/j.biopha.2018.11.051.","journal-title":"Biomed Pharmacother"},{"key":"9636_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3407","author":"B Obermeier","year":"2013","unstructured":"Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013. https:\/\/doi.org\/10.1038\/nm.3407.","journal-title":"Nat Med"},{"key":"9636_CR75","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)03173-X","author":"JF Caro","year":"1996","unstructured":"Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK, Considine RV. Decreased cerebrospinal-fluid\/serum leptin ratio in obesity: A possible mechanism for leptin resistance. Lancet. 1996. https:\/\/doi.org\/10.1016\/S0140-6736(96)03173-X.","journal-title":"Lancet"},{"key":"9636_CR76","doi-asserted-by":"crossref","first-page":"8878","DOI":"10.1073\/pnas.94.16.8878","volume":"94","author":"JL Halaas","year":"1997","unstructured":"Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci U S A. 1997;94:8878\u201383.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR77","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119171","author":"M Van Heek","year":"1997","unstructured":"Van Heek M, Compton DS, France CF, Tedesco RP, Fawzi AB, Graziano MP, Sybertz EJ, Strader CD, Davis HR. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest. 1997. https:\/\/doi.org\/10.1172\/JCI119171.","journal-title":"J Clin Invest"},{"key":"9636_CR78","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0196-9781(96)00025-3","volume":"17","author":"WA Banks","year":"1996","unstructured":"Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides. 1996;17:305\u201311.","journal-title":"Peptides"},{"key":"9636_CR79","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0196-9781(99)00139-4","volume":"20","author":"WA Banks","year":"1999","unstructured":"Banks WA, DiPalma CR, Farrell CL. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides. 1999;20:1341\u20135.","journal-title":"Peptides"},{"key":"9636_CR80","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201805-0879OC","author":"S Berger","year":"2019","unstructured":"Berger S, Pho H, Fleury-Curado T, et al. Intranasal leptin relieves sleep-disordered breathing in mice with diet-induced obesity. Am J Respir Crit Care Med. 2019. https:\/\/doi.org\/10.1164\/rccm.201805-0879OC.","journal-title":"Am J Respir Crit Care Med"},{"key":"9636_CR81","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2337\/diabetes.53.5.1253","volume":"53","author":"WA Banks","year":"2004","unstructured":"Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, Morley JE. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes. 2004;53:1253\u201360.","journal-title":"Diabetes"},{"key":"9636_CR82","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1210\/endo.139.8.6154","volume":"139","author":"C Bjorbaek","year":"1998","unstructured":"Bjorbaek C, Elmquist JK, Michl P, Ahima RS, van Bueren A, McCall AL, Flier JS. Expression of leptin receptor isoforms in rat brain microvessels. Endocrinology. 1998;139:3485\u201391.","journal-title":"Endocrinology"},{"key":"9636_CR83","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1046\/j.1471-4159.1998.71041761.x","volume":"71","author":"RJ Boado","year":"1998","unstructured":"Boado RJ, Golden PL, Levin N, Pardridge WM. Up-regulation of blood-brain barrier short-form leptin receptor gene products in rats fed a high fat diet. J Neurochem. 1998;71:1761\u20134.","journal-title":"J Neurochem"},{"key":"9636_CR84","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1210\/endo.143.3.8669","volume":"143","author":"SM Hileman","year":"2002","unstructured":"Hileman SM, Pierroz DD, Masuzaki H, Bjorbaek C, El-Haschimi K, Banks WA, Flier JS. Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. Endocrinology. 2002;143:775\u201383.","journal-title":"Endocrinology"},{"key":"9636_CR85","doi-asserted-by":"crossref","first-page":"5414","DOI":"10.1210\/en.2007-0655","volume":"148","author":"M Faouzi","year":"2007","unstructured":"Faouzi M, Leshan R, Bjornholm M, Hennessey T, Jones J, Munzberg H. Differential accessibility of circulating leptin to individual hypothalamic sites. Endocrinology. 2007;148:5414\u201323.","journal-title":"Endocrinology"},{"key":"9636_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.01.003","author":"EM Rodr\u00edguez","year":"2010","unstructured":"Rodr\u00edguez EM, Bl\u00e1zquez JL, Guerra M. The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: The former opens to the portal blood and the latter to the cerebrospinal fluid. Peptides. 2010. https:\/\/doi.org\/10.1016\/j.peptides.2010.01.003.","journal-title":"Peptides"},{"key":"9636_CR87","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/BF00211479","volume":"228","author":"B Krisch","year":"1983","unstructured":"Krisch B, Leonhardt H, Oksche A. The meningeal compartments of the median eminence and the cortex. A comparative analysis in the rat. Cell Tissue Res. 1983;228:597\u2013640.","journal-title":"Cell Tissue Res"},{"key":"9636_CR88","doi-asserted-by":"publisher","DOI":"10.1007\/s002219900289","author":"B Peruzzo","year":"2000","unstructured":"Peruzzo B, Pastor FE, Bl\u00e1zquez JL, Sch\u00f6bitz K, Pel\u00e1ez B, Amat P, Rodr\u00edguez EM. A second look at the barriers of the medial basal hypothalamus. Exp Brain Res. 2000. https:\/\/doi.org\/10.1007\/s002219900289.","journal-title":"Exp Brain Res"},{"key":"9636_CR89","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22273","author":"A Mullier","year":"2010","unstructured":"Mullier A, Bouret SG, Prevot V, Dehouck B. Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. J Comp Neurol. 2010. https:\/\/doi.org\/10.1002\/cne.22273.","journal-title":"J Comp Neurol"},{"key":"9636_CR90","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23355","author":"F Langlet","year":"2013","unstructured":"Langlet F, Mullier A, Bouret SG, Prevot V, Dehouck B. Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain. J Comp Neurol. 2013. https:\/\/doi.org\/10.1002\/cne.23355.","journal-title":"J Comp Neurol"},{"key":"9636_CR91","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23817","author":"S Yoo","year":"2020","unstructured":"Yoo S, Cha D, Kim S, Jiang L, Cooke P, Adebesin M, Wolfe A, Riddle R, Aja S, Blackshaw S. Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice. Glia. 2020. https:\/\/doi.org\/10.1002\/glia.23817.","journal-title":"Glia"},{"key":"9636_CR92","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cmet.2013.12.015","volume":"19","author":"E Balland","year":"2014","unstructured":"Balland E, Dam J, Langlet F, et al. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 2014;19:293\u2013301.","journal-title":"Cell Metab"},{"key":"9636_CR93","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00240","author":"S Yoo","year":"2019","unstructured":"Yoo S, Cha D, Kim DW, Hoang TV, Blackshaw S. Tanycyte-Independent Control of Hypothalamic Leptin Signaling. Front Neurosci. 2019. https:\/\/doi.org\/10.3389\/fnins.2019.00240.","journal-title":"Front Neurosci"},{"key":"9636_CR94","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3921","author":"MP Lun","year":"2015","unstructured":"Lun MP, Monuki ES, Lehtinen MK. Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci. 2015. https:\/\/doi.org\/10.1038\/nrn3921.","journal-title":"Nat Rev Neurosci"},{"key":"9636_CR95","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-018-0221-z","author":"L Harrison","year":"2019","unstructured":"Harrison L, Schriever SC, Feuchtinger A, Kyriakou E, Baumann P, Pfuhlmann K, Messias AC, Walch A, Tsch\u00f6p MH, Pfluger PT. Fluorescent blood\u2013brain barrier tracing shows intact leptin transport in obese mice. Int J Obes.\u00a02019.\u00a0https:\/\/doi.org\/10.1038\/s41366-018-0221-z.","journal-title":"Int J Obes"},{"key":"9636_CR96","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molmet.2017.12.001","volume":"8","author":"A Di Spiezio","year":"2018","unstructured":"Di Spiezio A, Sandin ES, Dore R, et al. The LepR-mediated leptin transport across brain barriers controls food reward. Mol Metab. 2018;8:13\u201322.","journal-title":"Mol Metab"},{"key":"9636_CR97","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218284110","author":"LE Olofsson","year":"2013","unstructured":"Olofsson LE, Unger EK, Cheung CC, Xu AW. Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance. Proc Natl Acad Sci U S A. 2013. https:\/\/doi.org\/10.1073\/pnas.1218284110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR98","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.060","author":"E Yulyaningsih","year":"2017","unstructured":"Yulyaningsih E, Rudenko IA, Valdearcos M, Dahl\u00e9n E, Vagena E, Chan A, Alvarez-Buylla A, Vaisse C, Koliwad SK, Xu AW. Acute Lesioning and Rapid Repair of Hypothalamic Neurons outside the Blood-Brain Barrier. Cell Rep. 2017. https:\/\/doi.org\/10.1016\/j.celrep.2017.05.060.","journal-title":"Cell Rep"},{"key":"9636_CR99","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390215","author":"RG Miller","year":"1996","unstructured":"Miller RG, Petajan JH, Bryan WW, Armon C, Barohn RJ, Goodpasture JC, Hoagland RJ, Parry GJ, Ross MA, Stromatt SC. A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. Ann Neurol. 1996. https:\/\/doi.org\/10.1002\/ana.410390215.","journal-title":"Ann Neurol"},{"key":"9636_CR100","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1001\/jama.289.14.1826","volume":"289","author":"MP Ettinger","year":"2003","unstructured":"Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. JAMA. 2003;289:1826\u201332.","journal-title":"JAMA"},{"key":"9636_CR101","doi-asserted-by":"publisher","DOI":"10.1038\/nm1383","author":"MJ Watt","year":"2006","unstructured":"Watt MJ, Dzamko N, Thomas WG, Rose-John S, Ernst M, Carling D, Kemp BE, Febbraio MA, Steinberg GR. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med. 2006. https:\/\/doi.org\/10.1038\/nm1383.","journal-title":"Nat Med"},{"key":"9636_CR102","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2335926100","author":"MW Sleeman","year":"2003","unstructured":"Sleeman MW, Garcia K, Liu R, Murray JD, Malinova L, Moncrieffe M, Yancopoulos GD, Wiegand SJ. Ciliary neurotrophic factor improves diabetic parameters and hepatic steatosis and increases basal metabolic rate in db\/db mice. Proc Natl Acad Sci U S A. 2003. https:\/\/doi.org\/10.1073\/pnas.2335926100.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR103","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00768","author":"J Perugini","year":"2019","unstructured":"Perugini J, Di Mercurio E, Tossetta G, Severi I, Monaco F, Reguzzoni M, Tomasetti M, Dani C, Cinti S, Giordano A. Biological Effects of Ciliary Neurotrophic Factor on hMADS Adipocytes. Front Endocrinol (Lausanne). 2019. https:\/\/doi.org\/10.3389\/fendo.2019.00768.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"9636_CR104","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00289","author":"M Senzacqua","year":"2016","unstructured":"Senzacqua M, Severi I, Perugini J, Acciarini S, Cinti S, Giordano A. Action of administered ciliary neurotrophic factor on the mouse dorsal vagal complex. Front Neurosci. 2016. https:\/\/doi.org\/10.3389\/fnins.2016.00289.","journal-title":"Front Neurosci"},{"key":"9636_CR105","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1073\/pnas.061034298","volume":"98","author":"PD Lambert","year":"2001","unstructured":"Lambert PD, Anderson KD, Sleeman MW, et al. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc Natl Acad Sci U S A. 2001;98:4652\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR106","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00140","author":"W Venema","year":"2020","unstructured":"Venema W, Severi I, Perugini J, Di Mercurio E, Mainardi M, Maffei M, Cinti S, Giordano A. Ciliary Neurotrophic Factor Acts on Distinctive Hypothalamic Arcuate Neurons and Promotes Leptin Entry Into and Action on the Mouse Hypothalamus. Front Cell Neurosci. 2020. https:\/\/doi.org\/10.3389\/fncel.2020.00140.","journal-title":"Front Cell Neurosci"},{"key":"9636_CR107","doi-asserted-by":"publisher","DOI":"10.1590\/s0001-37652001000200006","author":"MC Diamond","year":"2001","unstructured":"Diamond MC. Response of the brain to enrichment. An Acad Bras Cienc. 2001. https:\/\/doi.org\/10.1590\/s0001-37652001000200006.","journal-title":"An Acad Bras Cienc"},{"key":"9636_CR108","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(95)00216-2","author":"MR Rosenzweig","year":"1996","unstructured":"Rosenzweig MR, Bennett EL. Psychobiology of plasticity: Effects of training and experience on brain and behavior. Behav Brain Res. 1996. https:\/\/doi.org\/10.1016\/0166-4328(95)00216-2.","journal-title":"Behav Brain Res"},{"key":"9636_CR109","doi-asserted-by":"publisher","DOI":"10.1038\/35044558","author":"H van Praag","year":"2000","unstructured":"van Praag H, Kempermann G, Gage FH. Neural consequences of enviromental enrichment. Nat Rev Neurosci. 2000. https:\/\/doi.org\/10.1038\/35044558.","journal-title":"Nat Rev Neurosci"},{"key":"9636_CR110","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/438072","author":"M Mainardi","year":"2013","unstructured":"Mainardi M, Pizzorusso T, Maffei M. Environment, leptin sensitivity, and hypothalamic plasticity. Neural Plast. 2013. https:\/\/doi.org\/10.1155\/2013\/438072.","journal-title":"Neural Plast"},{"key":"9636_CR111","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1970","author":"J Nithianantharajah","year":"2006","unstructured":"Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006. https:\/\/doi.org\/10.1038\/nrn1970.","journal-title":"Nat Rev Neurosci"},{"key":"9636_CR112","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.12.004","author":"A Sale","year":"2009","unstructured":"Sale A, Berardi N, Maffei L. Enrich the environment to empower the brain. Trends Neurosci. 2009. https:\/\/doi.org\/10.1016\/j.tins.2008.12.004.","journal-title":"Trends Neurosci"},{"key":"9636_CR113","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(84)90098-0","author":"HB Katz","year":"1984","unstructured":"Katz HB, Davies CA. Effects of differential environments on the cerebral anatomy of rats as a function of previous and subsequent housing conditions. Exp Neurol. 1984. https:\/\/doi.org\/10.1016\/S0014-4886(84)90098-0.","journal-title":"Exp Neurol"},{"key":"9636_CR114","doi-asserted-by":"crossref","unstructured":"Sale A, Berardi N, Maffei L. Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiological reviews. 2014;94(1):189-234.","DOI":"10.1152\/physrev.00036.2012"},{"key":"9636_CR115","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911832107","author":"M Mainardi","year":"2010","unstructured":"Mainardi M, Scabia G, Vottari T, Santini F, Pinchera A, Maffei L, Pizzorusso T, Maffei M. A sensitive period for environmental regulation of eating behavior and leptin sensitivity. Proc Natl Acad Sci U S A. 2010. https:\/\/doi.org\/10.1073\/pnas.0911832107.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR116","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002790107","author":"S Stanley","year":"2010","unstructured":"Stanley S, Pinto S, Segal J, P\u00e9rez CA, Viale A, DeFalco J, Cai X, Heisler LK, Friedman JM. Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc Natl Acad Sci U S A. 2010. https:\/\/doi.org\/10.1073\/pnas.1002790107.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9636_CR117","doi-asserted-by":"publisher","DOI":"10.1038\/srep12517","author":"L Ruiz-Perera","year":"2015","unstructured":"Ruiz-Perera L, Muniz M, Vierci G, Bornia N, Baroncelli L, Sale A, Rossi FM. Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex. Sci Rep. 2015. https:\/\/doi.org\/10.1038\/srep12517.","journal-title":"Sci Rep"},{"key":"9636_CR118","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3741-04.2005","author":"M Sairanen","year":"2005","unstructured":"Sairanen M, Lucas G, Ernfors P, Castr\u00e9n M, Castr\u00e9n E. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci. 2005. https:\/\/doi.org\/10.1523\/JNEUROSCI.3741-04.2005.","journal-title":"J Neurosci"},{"key":"9636_CR119","doi-asserted-by":"publisher","unstructured":"Vetencourt JFM, Sale A, Viegi A, Baroncelli L, De Pasquale R, O\u2019Leary OF, Castr\u00e9n E, Maffei L.\u00a0The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science (80- ). 2008.\u00a0https:\/\/doi.org\/10.1126\/science.1150516.","DOI":"10.1126\/science.1150516"},{"key":"9636_CR120","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/54.2.321","author":"LL Darga","year":"1991","unstructured":"Darga LL, Carroll-Michals L, Botsford SJ, Lucas CP. Fluoxetine\u2019s effect on weight loss in obese subjects. Am J Clin Nutr. 1991. https:\/\/doi.org\/10.1093\/ajcn\/54.2.321.","journal-title":"Am J Clin Nutr"},{"key":"9636_CR121","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19886-x","author":"G Scabia","year":"2018","unstructured":"Scabia G, Barone I, Mainardi M, et al. The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF. Sci Rep. 2018. https:\/\/doi.org\/10.1038\/s41598-018-19886-x.","journal-title":"Sci Rep"},{"key":"9636_CR122","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1052-6","author":"I Barone","year":"2018","unstructured":"Barone I, Melani R, Mainardi M, et al. Fluoxetine Modulates the Activity of Hypothalamic POMC Neurons via mTOR Signaling. Mol Neurobiol. 2018. https:\/\/doi.org\/10.1007\/s12035-018-1052-6.","journal-title":"Mol Neurobiol"},{"key":"9636_CR123","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704","author":"N Hay","year":"2004","unstructured":"Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004. https:\/\/doi.org\/10.1101\/gad.1212704.","journal-title":"Genes Dev"},{"key":"9636_CR124","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12131","author":"CE Koch","year":"2014","unstructured":"Koch CE, Lowe C, Pretz D, Steger J, Williams LM, Tups A. High-fat diet induces leptin resistance in leptin-deficient mice. J Neuroendocrinol. 2014. https:\/\/doi.org\/10.1111\/jne.12131.","journal-title":"J Neuroendocrinol"},{"key":"9636_CR125","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00378","author":"M Maffei","year":"2019","unstructured":"Maffei M, Mainardi M. Editorial: Metabolic Mediators and Synapses: Linking Body Periphery to Neural Plasticity. Front Cell Neurosci. 2019. https:\/\/doi.org\/10.3389\/fncel.2019.00378.","journal-title":"Front Cell Neurosci"},{"key":"9636_CR126","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.237","author":"J Zhao","year":"2011","unstructured":"Zhao J, Bradfield JP, Zhang H, et al. Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity. 2011. https:\/\/doi.org\/10.1038\/oby.2011.237.","journal-title":"Obesity"},{"key":"9636_CR127","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.159","author":"J Zhao","year":"2009","unstructured":"Zhao J, Bradfield JP, Li M, et al. The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity. 2009. https:\/\/doi.org\/10.1038\/oby.2009.159.","journal-title":"Obesity"}],"container-title":["Reviews in Endocrine and Metabolic Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-021-09636-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11154-021-09636-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-021-09636-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T01:39:16Z","timestamp":1645666756000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11154-021-09636-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":127,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["9636"],"URL":"https:\/\/doi.org\/10.1007\/s11154-021-09636-2","relation":{},"ISSN":["1389-9155","1573-2606"],"issn-type":[{"value":"1389-9155","type":"print"},{"value":"1573-2606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"assertion":[{"value":"11 February 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Authors have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"\u00a0Conflict of interest"}}]}}