Open AccessGenetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
Author(s) -
Norheim Frode,
Chella Krishnan Karthickeyan,
Bjellaas Thomas,
Vergnes Laurent,
Pan Calvin,
Parks Brian W,
Meng Yonghong,
Lang Jennifer,
Ward James A,
Reue Karen,
Mehrabian Margarete,
Gundersen Thomas E,
Péterfy Miklós,
Dalen Knut T,
Drevon Christian A,
Hui Simon T,
Lusis Aldons J,
Seldin Marcus M
Publication year - 2021
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20209684
Subject(s) - biology , lipidome , steatosis , insulin resistance , phenotype , lipidomics , inbred strain , gene , genetic variation , fatty liver , genetics , lipid metabolism , genome wide association study , model organism , metabolomics , biochemistry , insulin , endocrinology , bioinformatics , medicine , single nucleotide polymorphism , genotype , disease
To elucidate the contributions of specific lipid species to metabolic traits, we integrated global hepatic lipid data with other omics measures and genetic data from a cohort of about 100 diverse inbred strains of mice fed a high‐fat/high‐sucrose diet for 8 weeks. Association mapping, correlation, structure analyses, and network modeling revealed pathways and genes underlying these interactions. In particular, our studies lead to the identification of Ifi203 and Map2k6 as regulators of hepatic phosphatidylcholine homeostasis and triacylglycerol accumulation, respectively. Our analyses highlight mechanisms for how genetic variation in hepatic lipidome can be linked to physiological and molecular phenotypes, such as microbiota composition.