Systems Genetic Analysis of Brown Adipose Tissue Function.
Michal Pravenec, Laura Saba, Vaclav Zidek, Vladimir Landa, Petr Mlejnek, Jan Silhavy, Miroslava Simakova, Hynak Strnad, Jaroslava Trnovska, Vojtech Skop, Martina Huttl, Irena Markova, Olena Oliyarnyk, Hana Malinska, Ludmila Kazdova, Harry Smith, Boris Tabakoff
Physiological genomics 2017 Nov 10Brown adipose tissue (BAT) has been suggested to play an important role in lipid and glucose metabolism in rodents and possibly also in humans. In the current study, we used genetic and correlation analyses in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), to identify genetic determinants of BAT function. Linkage analyses revealed a quantitative trait locus (QTL) associated with interscapular BAT mass on chromosome 4 and two closely linked QTLs associated with glucose oxidation and glucose incorporation into BAT lipids on chromosome 2. Using weighted gene co-expression network analysis (WGCNA) we identified 1,147 gene co-expression modules in the BAT from BXH/HXB rats and mapped their module eigengene QTLs. Through an unsupervised analysis, we identified modules related to BAT relative mass and function. The Coral4.1 co-expression module is associated with BAT relative mass (includes Cd36 highly connected gene) and the Darkseagreen co-expression module is associated with glucose incorporation into BAT lipids (includes Hiat1, Fmo5 and Sort1 highly connected transcripts). Because multiple statistical criteria were used to identify candidate modules, significance thresholds for individual tests were not adjusted for multiple comparisons across modules. In summary, a systems genetic analysis using genomic and quantitative transcriptomic and physiologic information has produced confirmation of several known genetic factors and significant insight into novel genetic components functioning in BAT and possibly contributing to traits characteristic of the metabolic syndrome. Copyright © 2017, Physiological Genomics.
Citation
Michal Pravenec, Laura Saba, Vaclav Zidek, Vladimir Landa, Petr Mlejnek, Jan Silhavy, Miroslava Simakova, Hynak Strnad, Jaroslava Trnovska, Vojtech Skop, Martina Huttl, Irena Markova, Olena Oliyarnyk, Hana Malinska, Ludmila Kazdova, Harry Smith, Boris Tabakoff. Systems Genetic Analysis of Brown Adipose Tissue Function. Physiological genomics. 2017 Nov 10:physiolgenomics.00091.2017
PMID: 29127223
View Full Text
