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Publication
Melanocortin-4 receptor mutations paradoxically reduce preference for palatable
foods.
Authors Panaro BL, Cone RD
Submitted By Submitted Externally on 7/28/2017
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2013
Date Published 4/23/2013
Volume : Pages 110 : 7050 - 5
PubMed Reference 23569235
Abstract Haploinsufficiency of the melanocortin-4 receptor (MC4R) results in melanocortin
obesity syndrome, the most common monogenic cause of severe early onset obesity
in humans. The syndrome, which produces measurable hyperphagia, has focused
attention on the role of MC4R in feeding behavior and macronutrient intake.
Studies show that inhibition of MC4R signaling can acutely increase the
consumption of high-fat foods. The current study examines the chronic feeding
preferences of mice with deletion of one or both alleles of the MC4R to model
the human syndrome. Using two-choice diet paradigms with high-fat or
high-carbohydrate foods alongside normal chow, we show, paradoxically, that
deletion of one allele has no effect, whereas deletion of both alleles of the
MC4R actually decreases preference for palatable high-fat and high-sucrose
foods, compared with wild-type mice. Nonetheless, we observed hyperphagic
behavior from increased consumption of the low-fat standard chow when either
heterozygous or homozygous mutant animals were presented with dietary variety.
Thus, decreased MC4R signaling in melanocortin obesity syndrome consistently
yields hyperphagia irrespective of the foods provided, but the hyperphagia
appears driven by variety and/or novelty, rather than by a preference for
high-fat or high-carbohydrate foodstuffs.




Strains
StrainDevelopment StatusCreation MethodOptions
C57BL/6-Mc4rtm1DhuPhenotyping ongoingknockout
View
C57BL/6-Mc4rtm1Dhu/+Phenotyping ongoingknockout
View


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