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
Affiliations
Jordan N. Reed
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Faten Hasan
Department of Kinesiology, University of Virginia School of Education and Human Development, Charlottesville, VA 22903, USA
Abhishek Karkar
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Dhanush Banka
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Jameson Hinkle
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Preeti Shastri
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Navya Srivastava
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Steven C. Scherping
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Sarah E. Newkirk
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
Heather A. Ferris
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Corresponding author
Bijoy K. Kundu
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Corresponding author
Sibylle Kranz
Department of Kinesiology, University of Virginia School of Education and Human Development, Charlottesville, VA 22903, USA; Corresponding author
Mete Civelek
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Corresponding author
Susanna R. Keller
Department of Medicine-Division of Endocrinology and Metabolism, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; Corresponding author
Summary: 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.
