Document Detail


Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both.
MedLine Citation:
PMID:  18984673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic loci for body weight and subphenotypes such as fat weight have been mapped repeatedly. However, the distinct effects of different loci and physiological interactions among different traits are often not accounted for in mapping studies. Here we used the method of structural equation modeling to identify the specific relationships between genetic loci and different phenotypes influencing body weight. Using this technique, we were able to distinguish genetic loci that affect adiposity from those that affect muscle growth. We examined the high body weight-selected mouse lines NMRI8 and DU6i and the intercross populations NMRI8 x DBA/2 and DU6i x DBA/2. Structural models help us understand whether genetic factors affect lean mass and fat mass pleiotropically or nonpleiotropically. Sex has direct effects on both fat and muscle weight but also influences fat weight indirectly via muscle weight. Three genetic loci identified in these two crosses showed exclusive effects on fat deposition, and five loci contributed exclusively to muscle weight. Two additional loci showed pleiotropic effects on fat and muscle weight, with one locus acting in both crosses. Fat weight and muscle weight were influenced by epistatic effects. We provide evidence that significant fat loci in strains selected for body weight contribute to fat weight both directly and indirectly via the influence on lean weight. These results shed new light on the action of genes in quantitative trait locus regions potentially influencing muscle and fat mass and thus controlling body weight as a composite trait.
Authors:
Gudrun A Brockmann; Shirng-Wern Tsaih; Christina Neuschl; Gary A Churchill; Renhua Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-04
Journal Detail:
Title:  Physiological genomics     Volume:  36     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-02-26     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  114-26     Citation Subset:  IM    
Affiliation:
Breeding Biology and Molecular Genetics, Institute of Animal Sciences, Humboldt-Universität zu Berlin, Invalidenstrasse 42, Berlin, Germany. gudrun.brockmann@agrar.hu-berlin.de
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / anatomy & histology
Animals
Body Weight / genetics*
Body Weights and Measures
Female
Male
Mice
Mice, Inbred Strains
Muscle, Skeletal / growth & development
Obesity / genetics*,  metabolism
Phenotype
Quantitative Trait Loci
Grant Support
ID/Acronym/Agency:
GM 076468/GM/NIGMS NIH HHS
Comments/Corrections

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