Vitamin D(3) 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.