Details

Autor(en) / Beteiligte

• Parks, Brian W.
• Sallam, Tamer
• Mehrabian, Margarete
• Psychogios, Nikolas
• Hui, Simon T.
• Norheim, Frode
• Castellani, Lawrence W.
• Rau, Christoph D.
• Pan, Calvin
• Phun, Jennifer
• Zhou, Zhenqi
• Yang, Wen-Pin
• Neuhaus, Isaac
• Gargalovic, Peter S.
• Kirchgessner, Todd G.
• Graham, Mark
• Lee, Richard
• Tontonoz, Peter
• Gerszten, Robert E.
• Hevener, Andrea L.
• Lusis, Aldons J.

Titel

Genetic Architecture of Insulin Resistance in the Mouse

Ist Teil von

• Cell metabolism, 2015-02, Vol.21 (2), p.334-347

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Insulin resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment, and disease pathology, the genetic basis of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates. Our results show dramatic variation in IR among strains of mice and widespread differences between sexes that are dependent on genotype. We uncover more than 15 genome-wide significant loci and validate a gene, Agpat5, associated with IR. We also integrate plasma metabolite levels and global gene expression from liver and adipose tissue to identify metabolite quantitative trait loci (mQTL) and expression QTL (eQTL), respectively. Our results provide a resource for analysis of interactions between diet, sex, and genetic background in IR. [Display omitted] •Dramatic variation in insulin resistance among inbred strains of mice•Widespread sex differences in insulin resistance that is dependent on genotype•Identification of 15 genetic loci associated with HOMA-IR and related traits•Identification and validation of Agpat5, a gene associated with insulin resistance Using a systems genetics analysis across more than 100 mouse strains to tackle the complex genetic basis of insulin resistance (IR), Parks et al. reveal interactions between diet, sex, and genetic background and identify multiple IR-associated genetic loci, further validating Agpat5 as a genetic factor contributing to IR.