Vitamin D3 supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR-/- and LDLR+/+ mice

Introduction: Fatty liver disease is prevalent in populations with high caloric intake. Nutritherapeutic approaches are being considered, such as supplementary Vitamin D-3, to improve aspects of metabolic syndrome, namely fatty liver disease, hyperlipidemia, and insulin resistance associated with obesity. Methods: We analyzed female LDLR-/- and LDLR+/+ mice on a 10-week diabetogenic diet for markers of fatty liver disease, metabolic strain, and inflammation. Results: The groups on a high fat high sugar diet with supplementary Vitamin D-3, in comparison with the groups on a high fat high sugar diet alone, showed improved transaminase levels, significantly less hypertriglyceridemia and hyperinsulinemia, and histologically, there was less pericentral hepatic steatosis. Levels of non-esterified fatty acids and lipid peroxidation products were significantly lower in the group supplemented with additional Vitamin D-3, as were systemic markers of inflammation (serum endotoxin and IL-6). M2 macrophage phenotype predominated in the group supplemented with additional Vitamin D-3. Beneficial changes were observed as early as five weeks' supplementation with Vitamin D-3 and extended to restoration of high fat high sugar diet induced decrease of bone mineral density. Conclusion: In summary, Vitamin D-3 was a significantly beneficial dietary additive to blunt a prediabetic phenotype in diet-induced obesity of female LDLR-/- and LDLR+/+ mice.