title: Genetic aspects of human obesity.
abstract: Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Larder
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Chung Thong
authors.initials: CT
authors.lastname: Lim
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address: apc36@cam.ac.uk.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Coll
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D009765:Obesity / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism
chemical_list: D011333:Pro-Opiomelanocortin
keywords: Bardet–Biedl syndrome; GWAS; Obesity; Prader–Willi syndrome; copy number variant; hypothalamus; leptin; melanocortin; whole exome sequencing