Creation of a genetic model of obesity in a teleost.
The adipostat is the mechanism by which the brain detects and maintains constant levels of energy stored in adipocytes in the form of lipids. Key elements of the adipostat include the adipocyte-derived hormone leptin that is expressed in proportion to energy levels and serves to communicate this information to the central nervous system and the central circuits, which sense and respond to leptin. Blockade of one of these circuits, the central melanocortin system, disrupts leptin action and causes a distinct obesity syndrome in mice and humans, characterized by increased adiposity as well as increased linear growth. We show here that transgenic zebrafish overexpressing the endogenous melanocortin antagonist agouti-related protein (AgRP) also exhibit obesity, increased linear growth, and adipocyte hypertrophy. These findings demonstrate that key elements of the adipostat originated before the evolution of mammals. Furthermore, transgenic overexpression of AgRP in zebrafish yields a new model system for the genetic analysis of energy homeostasis in a simple vertebrate system.
Song
Youngsup
Y
Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA.
Cone
Roger D
RD
D054369:Agouti-Related Protein; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D000242:Cyclic AMP / Q000502:physiology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D005813:Genes, Synthetic; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D008297:Male; D053486:Melanocortins / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics / Q000502:physiology; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D053486:Melanocortins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D014280:Triglycerides; D029961:Zebrafish Proteins; C461479:mc4r protein, zebrafish; D000242:Cyclic AMP