Obesity genes and the regulation of body fat content.
Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.
Weigle
D S
DS
Department of Medicine, University of Washington School of Medicine, Seattle, USA.
Kuijper
J L
JL
D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000473:pathology*; D054366:Agouti Signaling Protein; D000818:Animals; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D012527:Satiation; D015398:Signal Transduction / Q000235:genetics; D015431:Weight Loss / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D054366:Agouti Signaling Protein; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone; C098988:Tub protein, mouse; D000521:alpha-MSH; C029446:MSH receptor