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Genetic Architecture of Insulin Resistance in the Mouse
Open accessAbstract
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.
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“By examining global gene expression in multiple tissues and metabolites in plasma, they were able to identify pathways and genes contributing to diet-induced obesity and diabetes.”
From Multi-omics approaches to disease (2017) · cites this paper as [32]
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“For example, Parks and coworkers [31, 32] recently studied the effects of a high fat, high sucrose diet across about 100 different inbred strains of mice.”
From Multi-omics approaches to disease (2017) · cites this paper as [32]
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Metadata
- Authors
- Parks, B. W., Sallam, T., Mehrabian, M., Psychogios, N., Hui, S. T., Norheim, F., Castellani, L. W., Rau, C. D., Pan, C., Phun, J., Zhou, Z., Yang, W.-P., Neuhaus, I., Gargalovic, P. S., Kirchgessner, T. G., Graham, M., Lee, R., Tontonoz, P., Gerszten, R. E., Hevener, A. L., & Lusis, A. J.
- Affiliations
- University of California, Los Angeles (US)
- University of Oslo (NO)
- Bristol-Myers Squibb (United States) (US)
- Ionis Pharmaceuticals (United States) (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Corresponding author
- Parks, Brian W.
- Lusis, Aldons J.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 21
- Issue
- 2
- Pages
- 334-347
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4349439
- OpenAlex
- W2000653200
- Cited by
- 249
- References
- 53
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 26 · 2023: 36 · 2022: 25 · 2021: 22 · 2020: 31 · 2019: 26 · 2018: 19 · 2017: 16 · 2016: 9 · 2015: 8
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K99HL123021, P01HL090553, HL28481, R01HL081572, R00HL123021, T32HL069766, P01HL028481)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089109, P30DK041301, P30DK063491, R01DK081572)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- insulin resistance, genetic architecture, inbred mouse strains, sex differences, metabolite quantitative trait loci, expression quantitative trait loci, hepatic gene expression, adipose tissue gene expression, high-fat high-carbohydrate diet, genetic background
- MeSH terms
- Animals, Dietary Carbohydrates, Female, Genotype, Insulin Resistance, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Genetic Variation, 1-Acylglycerol-3-Phosphate O-Acyltransferase, Mice, Diet, High-Fat
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