Combined effects of genetic background and diet on mouse metabolism and gene expression

Jordan N Reed; Faten Hasan; Abhishek Karkar; Dhanush Banka; Jameson Hinkle; Preeti Shastri; Navya Srivastava; Steven C Scherping; Sarah E Newkirk; Heather A Ferris; Bijoy K Kundu; Sibylle Kranz; Mete Civelek; Susanna R Keller

doi:10.1016/j.isci.2024.111323

Combined effects of genetic background and diet on mouse metabolism and gene expression

iScience. 2024 Nov 4;27(12):111323. doi: 10.1016/j.isci.2024.111323. eCollection 2024 Dec 20.

Authors

Jordan N Reed^{1

2}, Faten Hasan³, Abhishek Karkar⁴, Dhanush Banka^{1

2}, Jameson Hinkle², Preeti Shastri⁴, Navya Srivastava^{1

5}, Steven C Scherping⁴, Sarah E Newkirk⁴, Heather A Ferris⁴, Bijoy K Kundu^{1

5}, Sibylle Kranz³, Mete Civelek^{1

2}, Susanna R Keller⁴

Affiliations

¹ Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
² Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
³ Department of Kinesiology, University of Virginia School of Education and Human Development, Charlottesville, VA 22903, USA.
⁴ Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
⁵ Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.

Abstract

In humans, dietary patterns impact weight and metabolism differentially across individuals. To uncover genetic determinants for differential dietary effects, we subjected four genetically diverse mouse strains to humanized diets (American, Mediterranean, vegetarian, and vegan) with similar macronutrient composition, and performed body weight, metabolic parameter, and RNA-seq analysis. We observed pronounced diet- and strain-dependent effects on weight, and triglyceride and insulin levels. Differences in fat mass, adipose tissue, and skeletal muscle glucose uptake, and gene expression changes in most tissues were strain-dependent. In visceral adipose tissue, ∼400 genes responded to diet in a strain-dependent manner, many of them in metabolite transport and lipid metabolism pathways and several previously identified to modify diet effects in humans. Thus, genetic background profoundly impacts metabolism, though chosen dietary patterns modify the strong genetic effects. This study paves the way for future mechanistic investigations into strain-diet interactions in mice and translation to precision nutrition in humans.

Keywords: Diet; Genetics; Model organism; Transcriptomics.