Maternal Liver Metabolic Response to Chronic Vitamin D Deficiency Is Determined by Mouse Strain Genetic Background

• Published in: Current developments in nutrition 2020-08, Vol.4 (8), p.1
• Main Authors: Xue, Jing, Hutchins, Elizabeth K, Elnagheeb, Marwa, Li, Yi, Valdar, William, McRitchie, Susan, Sumner, Susan, Ideraabdullah, Folami Y
• Format: Article
• Language: English
• Subjects: Complications and side effects; Health aspects; Liver; Vitamin D deficiency
• ISSN: 2475-2991; 2475-2991

Background: Liver metabolite concentrations have the potential to be key biomarkers of systemic metabolic dysfunction and overall health. However, for most conditions we do not know the extent to which genetic differences regulate susceptibility to metabolic responses. This limits our ability to detect and diagnose effects in heterogeneous populations. Objectives: Here, we investigated the extent to which naturally occurring genetic differences regulate maternal liver metabolic response to vitamin D deficiency (VDD), particularly during perinatal periods when such changes can adversely affect maternal and fetal health. Methods: We used a panel of 8 inbred Collaborative Cross (CC) mouse strains, each with a different genetic background (72 dams, 3-6/treatment group, per strain). We identified robust maternal liver metabolic responses to vitamin D depletion before and during gestation and lactation using a vitamin-D-deficient (VDD; 0 IU vitamin D3/kg) or -sufficient diet (1000 IU vitamin D3/kg). We then identified VDD-induced metabolite changes influenced by strain genetic background. Results: We detected a significant VDD effect by orthogonal partial least squares discriminant analysis (Q2 = 0.266, pQ2 = 0.002): primarily, altered concentrations of 78 metabolites involved in lipid, amino acid, and nucleotide metabolism (variable importance to projection score >1.5). Metabolites in unsaturated fatty acid and glycerophospholipid metabolism pathways were significantly enriched [False Discovery Rate (FDR)