Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Abstract 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, corre...

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Main Authors:	Frode Norheim, Karthickeyan Chella Krishnan, Thomas Bjellaas, Laurent Vergnes, Calvin Pan, Brian W Parks, Yonghong Meng, Jennifer Lang, James A Ward, Karen Reue, Margarete Mehrabian, Thomas E Gundersen, Miklós Péterfy, Knut T Dalen, Christian A Drevon, Simon T Hui, Aldons J Lusis, Marcus M Seldin
Format:	Article
Language:	English
Published:	Wiley 2021-01-01
Series:	Molecular Systems Biology
Subjects:	genome‐wide association studies hepatic lipidome Hybrid Mouse Diversity Panel non‐alcoholic fatty liver disease quantitative trait loci for lipids
Online Access:	https://doi.org/10.15252/msb.20209684

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spelling	doaj-79a471c7fc2a4e9faa35faa4f62212342021-08-02T23:39:51ZengWileyMolecular Systems Biology1744-42922021-01-01171n/an/a10.15252/msb.20209684Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosisFrode Norheim0Karthickeyan Chella Krishnan1Thomas Bjellaas2Laurent Vergnes3Calvin Pan4Brian W Parks5Yonghong Meng6Jennifer Lang7James A Ward8Karen Reue9Margarete Mehrabian10Thomas E Gundersen11Miklós Péterfy12Knut T Dalen13Christian A Drevon14Simon T Hui15Aldons J Lusis16Marcus M Seldin17Division of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USAVitas AS Oslo NorwayDepartment of Human Genetics University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADepartment of Nutritional Sciences University of Wisconsin‐Madison Madison WI USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADepartment of Human Genetics University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USAVitas AS Oslo NorwayDivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADepartment of Nutrition Institute of Basic Medical Sciences Faculty of Medicine University of Oslo Oslo NorwayDepartment of Nutrition Institute of Basic Medical Sciences Faculty of Medicine University of Oslo Oslo NorwayDivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USADivision of Cardiology Department of Medicine University of California at Los Angeles Los Angeles CA USAAbstract 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.https://doi.org/10.15252/msb.20209684genome‐wide association studieshepatic lipidomeHybrid Mouse Diversity Panelnon‐alcoholic fatty liver diseasequantitative trait loci for lipids
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Frode Norheim Karthickeyan Chella Krishnan Thomas Bjellaas Laurent Vergnes Calvin Pan Brian W Parks Yonghong Meng Jennifer Lang James A Ward Karen Reue Margarete Mehrabian Thomas E Gundersen Miklós Péterfy Knut T Dalen Christian A Drevon Simon T Hui Aldons J Lusis Marcus M Seldin
spellingShingle	Frode Norheim Karthickeyan Chella Krishnan Thomas Bjellaas Laurent Vergnes Calvin Pan Brian W Parks Yonghong Meng Jennifer Lang James A Ward Karen Reue Margarete Mehrabian Thomas E Gundersen Miklós Péterfy Knut T Dalen Christian A Drevon Simon T Hui Aldons J Lusis Marcus M Seldin Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis Molecular Systems Biology genome‐wide association studies hepatic lipidome Hybrid Mouse Diversity Panel non‐alcoholic fatty liver disease quantitative trait loci for lipids
author_facet	Frode Norheim Karthickeyan Chella Krishnan Thomas Bjellaas Laurent Vergnes Calvin Pan Brian W Parks Yonghong Meng Jennifer Lang James A Ward Karen Reue Margarete Mehrabian Thomas E Gundersen Miklós Péterfy Knut T Dalen Christian A Drevon Simon T Hui Aldons J Lusis Marcus M Seldin
author_sort	Frode Norheim
title	Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
title_short	Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
title_full	Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
title_fullStr	Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
title_full_unstemmed	Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
title_sort	genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis
publisher	Wiley
series	Molecular Systems Biology
issn	1744-4292
publishDate	2021-01-01
description	Abstract 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.
topic	genome‐wide association studies hepatic lipidome Hybrid Mouse Diversity Panel non‐alcoholic fatty liver disease quantitative trait loci for lipids
url	https://doi.org/10.15252/msb.20209684
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Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

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