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Publication
Genetic control of obesity, glucose homeostasis, dyslipidemia and fatty liver in
a mouse model of diet-induced metabolic syndrome.
Authors Sinasac DS, Riordan JD, Spiezio SH, Yandell BS, Croniger CM, Nadeau JH
Submitted By Colleen Croniger on 10/15/2015
Status In press
Journal International journal of obesity (2005)
Year 2015
Date Published 9/18/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference 26381349
Abstract Both genetic and dietary factors contribute to the metabolic syndrome (MetS) in
humans and animal models. Characterizing their individual roles as well as
relationships among these factors is critical for understanding MetS
pathogenesis and developing effective therapies. By studying phenotypic
responsiveness to high-risk versus control diet in two inbred mouse strains and
their derivatives, we estimated the relative contributions of diet and genetic
background to MetS, characterized strain-specific combinations of MetS
conditions, and tested genetic and phenotypic complexity on a single substituted
chromosome., Ten measures of metabolic health were assessed in susceptible
C57BL/6?J and resistant A/J male mice fed either a control or a high-fat,
high-sucrose (HFHS) diet, permitting estimates of the relative influences of
strain, diet and strain-diet interactions for each trait. The same traits were
measured in a panel of C57BL/6?J (B6)-Chr(A/J) chromosome substitution strains
(CSSs) fed the HFHS diet, followed by characterization of interstrain
relationships, covariation among metabolic traits and quantitative trait loci
(QTLs) on Chromosome 10., We identified significant genetic contributions to
nine of ten metabolic traits and significant dietary influence on eight.
Significant strain-diet interaction effects were detected for four traits.
Although a range of HFHS-induced phenotypes were observed among the CSSs,
significant associations were detected among all traits but one. Strains were
grouped into three clusters based on overall phenotype and specific CSSs were
identified with distinct and reproducible trait combinations. Finally, several
Chr10 regions were shown to control the severity of MetS conditions., Generally
strong genetic and dietary effects validate these CSSs as a multifactorial model
of MetS. Although traits tended to segregate together, considerable phenotypic
heterogeneity suggests that underlying genetic factors influence their
co-occurrence and severity. Identification of multiple QTLs within and among
strains highlights both the complexity of genetically regulated, diet-induced
MetS and the ability of CSSs to prioritize candidate loci for mechanistic
studies.International Journal of Obesity advance online publication, 13 October
2015; doi:10.1038/ijo.2015.184.




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