{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:33:07Z","timestamp":1784255587148,"version":"3.55.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rev Endocr Metab Disord"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypothalamic circuits play a critical role in the regulation of energy homeostasis, a function that is essential for survival. Lesions of the hypothalamus in animals can cause weight gain or weight loss depending on their precise anatomical location and the chemical nature of circuits which are disrupted. Here, we discuss how human genetic disorders which impair the function of key molecular components of these hypothalamic circuits cause hyperphagia and obesity. The detailed molecular and physiological characterisation of these disorders provides direct insights into the mechanisms by which hypothalamic circuits and their projections regulate human physiology and behaviour. Increasingly, the finding of a genetic cause for a person\u2019s obesity can inform clinical care and the use of targeted therapies.<\/jats:p>\n                  <jats:p>Clinical trial number: not applicable.<\/jats:p>","DOI":"10.1007\/s11154-026-10050-9","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:30:25Z","timestamp":1779949825000},"page":"617-623","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypothalamic obesity"],"prefix":"10.1007","volume":"27","author":[{"given":"Ismaa Sadaf","family":"Farooqi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O\u2019Rahilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"10050_CR1","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1126\/science.adl3437","volume":"382","author":"M Maroso","year":"2023","unstructured":"Maroso M, Stern P. Small and mighty: The hypothalamus. Science. 2023;382:386\u20137.","journal-title":"Science"},{"key":"10050_CR2","first-page":"1276","volume":"59","author":"GC Kennedy","year":"1966","unstructured":"Kennedy GC. The hypothalamus and obesity. Proc R Soc Med. 1966;59:1276\u20137.","journal-title":"Proc R Soc Med"},{"key":"10050_CR3","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1002\/ar.1090780203","volume":"78","author":"AW Hetherington","year":"1940","unstructured":"Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. Anat Rec. 1940;78:149\u201372.","journal-title":"Anat Rec"},{"key":"10050_CR4","first-page":"123","volume":"24","author":"BK Anand","year":"1951","unstructured":"Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J Biol Med. 1951;24:123\u201340.","journal-title":"Yale J Biol Med"},{"key":"10050_CR5","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1126\/science.705344","volume":"202","author":"SP Grossman","year":"1978","unstructured":"Grossman SP, Dacey D, Halaris AE, Collier T, Routtenberg A. Aphagia and Adipsia After Preferential Destruction of Nerve Cell Bodies in Hypothalamus. Science. 1978;202:537\u20139.","journal-title":"Science"},{"key":"10050_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.cell.2015.03.008","volume":"161","author":"AA van der Klaauw","year":"2015","unstructured":"van der Klaauw AA, Farooqi IS. The Hunger Genes: Pathways to Obesity. Cell. 2015;161:119\u201332.","journal-title":"Cell"},{"key":"10050_CR7","doi-asserted-by":"publisher","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 Metabol. 2015;22:962\u201370.","journal-title":"Cell Metabol"},{"key":"10050_CR8","doi-asserted-by":"publisher","first-page":"eabl7398","DOI":"10.1126\/science.abl7398","volume":"381","author":"JC Br\u00fcning","year":"2023","unstructured":"Br\u00fcning JC, Fenselau H. Integrative neurocircuits that control metabolism and food intake. Science. 2023;381:eabl7398.","journal-title":"Science"},{"key":"10050_CR9","doi-asserted-by":"publisher","first-page":"e5370","DOI":"10.1371\/journal.pone.0005370","volume":"4","author":"J Guo","year":"2009","unstructured":"Guo J, Jou W, Gavrilova O, Hall KD. Persistent diet-induced obesity in male C57BL\/6 mice resulting from temporary obesigenic diets. PLoS ONE. 2009;4:e5370.","journal-title":"PLoS ONE"},{"key":"10050_CR10","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1242\/dmm.008698","volume":"4","author":"JR Speakman","year":"2011","unstructured":"Speakman JR, et al. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011;4:733\u201345.","journal-title":"Dis Model Mech"},{"key":"10050_CR11","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1007\/BF01221857","volume":"9","author":"DL Coleman","year":"1973","unstructured":"Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia. 1973;9:294\u20138.","journal-title":"Diabetologia"},{"key":"10050_CR12","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1113\/jphysiol.1959.sp006145","volume":"145","author":"GR Hervey","year":"1959","unstructured":"Hervey GR. The effects of lesions in the hypothalamus in parabiotic rats. J Physiol. 1959;145:336\u201352.","journal-title":"J Physiol"},{"key":"10050_CR13","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/372425a0","volume":"372","author":"Y Zhang","year":"1994","unstructured":"Zhang Y, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425\u201332.","journal-title":"Nature"},{"key":"10050_CR14","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1126\/science.7624777","volume":"269","author":"JL Halaas","year":"1995","unstructured":"Halaas JL, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269:543\u20136.","journal-title":"Science"},{"key":"10050_CR15","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1126\/science.7624776","volume":"269","author":"MA Pelleymounter","year":"1995","unstructured":"Pelleymounter MA, et al. Effects of the obese gene product on body weight regulation in ob\/ob mice. Science. 1995;269:540\u20133.","journal-title":"Science"},{"key":"10050_CR16","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1126\/science.7624778","volume":"269","author":"LA Campfield","year":"1995","unstructured":"Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995;269:546\u20139.","journal-title":"Science"},{"key":"10050_CR17","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/382250a0","volume":"382","author":"RS Ahima","year":"1996","unstructured":"Ahima RS, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382:250\u20132.","journal-title":"Nature"},{"key":"10050_CR18","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/cne.22025","volume":"514","author":"MM Scott","year":"2009","unstructured":"Scott MM, et al. Leptin targets in the mouse brain. J Comp Neurol. 2009;514:518\u201332.","journal-title":"J Comp Neurol"},{"key":"10050_CR19","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3389\/fnins.2017.00224","volume":"11","author":"R Haddad-T\u00f3volli","year":"2017","unstructured":"Haddad-T\u00f3volli R, Dragano NRV, Ramalho AFS, Velloso LA. Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control. Front Neurosci. 2017;11:224.","journal-title":"Front Neurosci"},{"key":"10050_CR20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/385165a0","volume":"385","author":"W Fan","year":"1997","unstructured":"Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385:165\u20138.","journal-title":"Nature"},{"key":"10050_CR21","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0092-8674(00)81865-6","volume":"88","author":"D Huszar","year":"1997","unstructured":"Huszar D, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88:131\u201341.","journal-title":"Cell"},{"key":"10050_CR22","doi-asserted-by":"publisher","first-page":"E827","DOI":"10.1152\/ajpendo.00670.2007","volume":"294","author":"JW Hill","year":"2008","unstructured":"Hill JW, Elmquist JK, Elias CF. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 2008;294:E827\u2013832.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10050_CR23","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.neuron.2017.06.014","volume":"95","author":"ML Andermann","year":"2017","unstructured":"Andermann ML, Lowell BB. Toward a Wiring Diagram Understanding of Appetite Control. Neuron. 2017;95:757\u201378.","journal-title":"Neuron"},{"key":"10050_CR24","doi-asserted-by":"crossref","unstructured":"Yang F, Zhao S, Wang P, Xiang W. Hypothalamic neuroendocrine integration of reproduction and metabolism in mammals. J Endocrinol. 2023;258.","DOI":"10.1530\/JOE-23-0079"},{"key":"10050_CR25","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/B978-0-12-820107-7.00009-4","volume":"180","author":"S Fischer","year":"2021","unstructured":"Fischer S. The hypothalamus in anxiety disorders. Handb Clin Neurol. 2021;180:149\u201360.","journal-title":"Handb Clin Neurol"},{"key":"10050_CR26","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/43185","volume":"387","author":"CT Montague","year":"1997","unstructured":"Montague CT, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387:903\u20138.","journal-title":"Nature"},{"key":"10050_CR27","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1056\/NEJMc1501146","volume":"372","author":"P Fischer-Posovszky","year":"2015","unstructured":"Fischer-Posovszky P, Funcke J-B, Wabitsch M. Biologically inactive leptin and early-onset extreme obesity. N Engl J Med. 2015;372:1266\u20137.","journal-title":"N Engl J Med"},{"key":"10050_CR28","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1056\/NEJMoa2204041","volume":"388","author":"J-B Funcke","year":"2023","unstructured":"Funcke J-B, et al. Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity. N Engl J Med. 2023;388:2253\u201361.","journal-title":"N Engl J Med"},{"key":"10050_CR29","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1172\/JCI0215693","volume":"110","author":"IS Farooqi","year":"2002","unstructured":"Farooqi IS, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine\/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002;110:1093\u2013103.","journal-title":"J Clin Invest"},{"key":"10050_CR30","doi-asserted-by":"publisher","first-page":"101187","DOI":"10.1016\/j.xcrm.2023.101187","volume":"4","author":"S Saeed","year":"2023","unstructured":"Saeed S, et al. High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor. Cell Rep Med. 2023;4:101187.","journal-title":"Cell Rep Med"},{"key":"10050_CR31","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1056\/NEJMoa063988","volume":"356","author":"IS Farooqi","year":"2007","unstructured":"Farooqi IS, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med. 2007;356:237\u201347.","journal-title":"N Engl J Med"},{"key":"10050_CR32","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1210\/clinem\/dgae149","volume":"109","author":"J von Schnurbein","year":"2024","unstructured":"von Schnurbein J, et al. Classification of Congenital Leptin Deficiency. J Clin Endocrinol Metab. 2024;109:2602\u201316.","journal-title":"J Clin Endocrinol Metab"},{"key":"10050_CR33","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1056\/NEJM199909163411204","volume":"341","author":"IS Farooqi","year":"1999","unstructured":"Farooqi IS, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341:879\u201384.","journal-title":"N Engl J Med"},{"key":"10050_CR34","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/S2213-8587(20)30364-8","volume":"8","author":"K Cl\u00e9ment","year":"2020","unstructured":"Cl\u00e9ment K, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020;8:960\u201370.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10050_CR35","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/509","volume":"19","author":"H Krude","year":"1998","unstructured":"Krude H, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19:155\u20137.","journal-title":"Nat Genet"},{"key":"10050_CR36","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/s41586-021-04088-9","volume":"599","author":"BYH Lam","year":"2021","unstructured":"Lam BYH, et al. MC3R links nutritional state to childhood growth and the timing of puberty. Nature. 2021;599:436\u201341.","journal-title":"Nature"},{"key":"10050_CR37","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1056\/NEJMoa1512693","volume":"375","author":"P K\u00fchnen","year":"2016","unstructured":"K\u00fchnen P, et al. Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. N Engl J Med. 2016;375:240\u20136.","journal-title":"N Engl J Med"},{"key":"10050_CR38","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.2337\/db06-0214","volume":"55","author":"IS Farooqi","year":"2006","unstructured":"Farooqi IS, et al. Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes. 2006;55:2549\u201353.","journal-title":"Diabetes"},{"key":"10050_CR39","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/ng0797-303","volume":"16","author":"RS Jackson","year":"1997","unstructured":"Jackson RS, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 1997;16:303\u20136.","journal-title":"Nat Genet"},{"key":"10050_CR40","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1056\/NEJM199511233332104","volume":"333","author":"S O\u2019Rahilly","year":"1995","unstructured":"O\u2019Rahilly S, et al. Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med. 1995;333:1386\u201390.","journal-title":"N Engl J Med"},{"key":"10050_CR41","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.cell.2018.12.009","volume":"176","author":"AA van der Klaauw","year":"2019","unstructured":"van der Klaauw AA, et al. Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance. Cell. 2019;176:729\u2013e74218.","journal-title":"Cell"},{"key":"10050_CR42","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1038\/s41467-019-08737-6","volume":"10","author":"Y Yang","year":"2019","unstructured":"Yang Y, et al. Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis. Nat Commun. 2019;10:1718.","journal-title":"Nat Commun"},{"key":"10050_CR43","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.cmet.2020.05.007","volume":"31","author":"G Marenne","year":"2020","unstructured":"Marenne G, et al. Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription. Cell Metab. 2020;31:1107\u2013e111912.","journal-title":"Cell Metab"},{"key":"10050_CR44","doi-asserted-by":"publisher","first-page":"e2532","DOI":"10.1210\/clinem\/dgac067","volume":"107","author":"TM Cacciottolo","year":"2022","unstructured":"Cacciottolo TM, et al. Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities. J Clin Endocrinol Metab. 2022;107:e2532\u201344.","journal-title":"J Clin Endocrinol Metab"},{"key":"10050_CR45","doi-asserted-by":"publisher","first-page":"eadl2675","DOI":"10.1126\/sciadv.adl2675","volume":"10","author":"H Liu","year":"2024","unstructured":"Liu H, et al. Neural circuits expressing the serotonin 2\u00a0C receptor regulate memory in mice and humans. Sci Adv. 2024;10:eadl2675.","journal-title":"Sci Adv"},{"key":"10050_CR46","doi-asserted-by":"crossref","unstructured":"Li Y et al. Loss of transient receptor potential channel 5 causes obesity and postpartum depression. Cell. 2024;0.","DOI":"10.1210\/jendso\/bvae163.1190"},{"key":"10050_CR47","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41591-021-01349-y","volume":"27","author":"KH Wade","year":"2021","unstructured":"Wade KH, et al. Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort. Nat Med. 2021;27:1088\u201396.","journal-title":"Nat Med"},{"key":"10050_CR48","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/2404","volume":"20","author":"GS Yeo","year":"1998","unstructured":"Yeo GS, et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 1998;20:111\u20132.","journal-title":"Nat Genet"},{"key":"10050_CR49","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/2407","volume":"20","author":"C Vaisse","year":"1998","unstructured":"Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet. 1998;20:113\u20134.","journal-title":"Nat Genet"},{"key":"10050_CR50","doi-asserted-by":"publisher","first-page":"E181","DOI":"10.1210\/jc.2010-1369","volume":"96","author":"CE Martinelli","year":"2011","unstructured":"Martinelli CE, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab. 2011;96:E181\u2013188.","journal-title":"J Clin Endocrinol Metab"},{"key":"10050_CR51","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41591-025-03913-2","volume":"31","author":"P Bhatnagar","year":"2025","unstructured":"Bhatnagar P, et al. Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency. Nat Med. 2025;31:3294\u20136.","journal-title":"Nat Med"},{"key":"10050_CR52","doi-asserted-by":"publisher","first-page":"E1023","DOI":"10.1210\/jc.2011-3432","volume":"97","author":"IJ Hatoum","year":"2012","unstructured":"Hatoum IJ, et al. Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery. J Clin Endocrinol Metab. 2012;97:E1023\u20131031.","journal-title":"J Clin Endocrinol Metab"},{"key":"10050_CR53","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1056\/NEJMoa2103329","volume":"385","author":"Mendes de Oliveira Edson","year":"2021","unstructured":"Mendes de Oliveira Edson. Obesity-Associated GNAS Mutations and the Melanocortin Pathway. N Engl J Med. 2021;385:1581\u201392.","journal-title":"N Engl J Med"},{"key":"10050_CR54","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41588-017-0023-6","volume":"50","author":"S Saeed","year":"2018","unstructured":"Saeed S, et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nat Genet. 2018;50:175\u20139.","journal-title":"Nat Genet"},{"key":"10050_CR55","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/s41588-017-0022-7","volume":"50","author":"N Grarup","year":"2018","unstructured":"Grarup N, et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nat Genet. 2018;50:172\u20134.","journal-title":"Nat Genet"},{"key":"10050_CR56","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41588-017-0020-9","volume":"50","author":"JE Siljee","year":"2018","unstructured":"Siljee JE, et al. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nat Genet. 2018;50:180\u20135.","journal-title":"Nat Genet"},{"key":"10050_CR57","doi-asserted-by":"publisher","first-page":"eadu4315","DOI":"10.1126\/scisignal.adu4315","volume":"18","author":"A Jamaluddin","year":"2025","unstructured":"Jamaluddin A, et al. The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling. Sci Signal. 2025;18:eadu4315.","journal-title":"Sci Signal"},{"key":"10050_CR58","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1172\/JCI68016","volume":"123","author":"S Ramachandrappa","year":"2013","unstructured":"Ramachandrappa S, et al. Rare variants in single-minded 1 (SIM1) are associated with severe obesity. J Clin Invest. 2013;123:3042\u201350.","journal-title":"J Clin Invest"},{"key":"10050_CR59","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1016\/j.molmet.2017.08.006","volume":"6","author":"L Moir","year":"2017","unstructured":"Moir L, et al. Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety. Mol Metab. 2017;6:1419\u201328.","journal-title":"Mol Metab"},{"key":"10050_CR60","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/nature08689","volume":"463","author":"EG Bochukova","year":"2010","unstructured":"Bochukova EG, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463:666\u201370.","journal-title":"Nature"},{"key":"10050_CR61","doi-asserted-by":"crossref","unstructured":"Moir, L. et al. Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety. Mol Metab. 2017;6:1419\u201328.","DOI":"10.1016\/j.molmet.2017.08.006"},{"key":"10050_CR62","doi-asserted-by":"crossref","unstructured":"Bochukova, E. G. et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463:666\u2013670.","DOI":"10.1038\/nature08689"},{"key":"10050_CR63","doi-asserted-by":"crossref","unstructured":"Doche, M. E. et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest. 2012;122:4732\u201336.","DOI":"10.1172\/JCI62696"},{"key":"10050_CR64","doi-asserted-by":"crossref","unstructured":"Jiang, L. et al. Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression. FASEB J. 2018;32:1830\u201340.","DOI":"10.1096\/fj.201700831R"},{"key":"10050_CR65","doi-asserted-by":"crossref","unstructured":"Flores, A. et al. Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance. Diabetes. 2019;68:2049\u201362.","DOI":"10.2337\/db19-0608"}],"container-title":["Reviews in Endocrine and Metabolic Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-026-10050-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11154-026-10050-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-026-10050-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:02:46Z","timestamp":1780902166000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11154-026-10050-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10050"],"URL":"https:\/\/doi.org\/10.1007\/s11154-026-10050-9","relation":{},"ISSN":["1389-9155","1573-2606"],"issn-type":[{"value":"1389-9155","type":"print"},{"value":"1573-2606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"assertion":[{"value":"6 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}