Study design and phenotypic diversity across strain, diet, and sex
(A) Scheme of the phenotyping pipeline of the study. Nine mouse inbred strains were tested (C57BL/6J, DBA/2J, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HILtJ, WSB/EiJ, CAST/EiJ, and PWK/PhJ). Five females or five males per diet (CD or HFD) were measured per strain. Five mice per condition were fed an HFD from 8 to 21 weeks of age with CD matched animals. Respiration, tolerance to glucose and cold, exercise capacity, and spontaneous activity were tested. Mice were sacrificed at 21 weeks of age after an overnight fast, and organ collection was performed.
(B) Schematic of the liver molecular phenotyping and data analysis. Livers were used for RNA-Seq and measurements of mitochondrial activity.
(C) Heatmap of the effects of diet on a selection of measured metabolic traits, in males or females. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, t test (HFD versus CD), corrected for multiple testing with the Benjamin-Hochberg false discovery rate (BH-FDR) procedure.