Lessons from extreme human obesity: monogenic disorders.
Human obesity has a strong genetic component. Most genes that influence an individual's predisposition to gain weight are not yet known. However, the study of extreme human obesity caused by single gene defects has provided a glimpse into the long-term regulation of body weight. These monogenic obesity disorders have confirmed that the hypothalamic leptin-melanocortin system is critical for energy balance in humans, because disruption of these pathways causes the most severe obesity phenotypes. Approximately 20 different genes and at least three different mechanisms have been implicated in monogenic causes of obesity; however, they account for fewer than 5% of all severe obesity cases. This finding suggests that the genetic basis for human obesity is likely to be extremely heterogeneous, with contributions from numerous genes acting by various, yet undiscovered, molecular mechanisms.
Ranadive
Sayali A
SA
Department of Pediatrics, Division of Endocrinology, University of California San Francisco, 513 Parnassus Avenue, Room S672D, San Francisco, CA 94143-0434, USA.
Vaisse
Christian
C
D020788:Bardet-Biedl Syndrome / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D045664:Proprotein Convertase 1 / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D011333:Pro-Opiomelanocortin; D045664:Proprotein Convertase 1; D044105:Receptor, Melanocortin, Type 4; D054411:Receptors, Leptin; D012097:Repressor Proteins; C470072:MC4R protein, human; C491094:SIM1 protein, human
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