Improvement of Metabolic Parameters in Mice Supplemented with Vitamin D throughout Life

Abstract

Rationale Metabolic endotoxemia contributes to chronic inflammation and adiposity, which may result in diabetes progression. We showed that healthy mice receiving low vs high vitamin D (25 vs 5000 IU/kg diet) from conception increased serum LPS at adulthood. This study determined if lifelong exposure to similar vitamin D levels in utero up to 6 months of age protects against adverse metabolic effects of a high fat diet. Methods Three-week old C57BL/6J dams were fed a modified AIN93G diet with high (H) or low (L) vitamin D during pregnancy and lactation until postnatal day (PND) 15, when a high fat diet (44% fat, 36% carbohydrates) was fed. On PND 21, male pups remained on their respective diets (LL or HH), or were switched (LH or HL). At 6 months, serum LPS, glucose and insulin concentrations were determined (ELISA) following an oral glucose tolerance test, and organs were weighed. Results High vitamin D resulted in lower pup weights at weaning (LD: 9.54 ± 0.16 vs. HD: 9.03 ± 0.15; p=0.02) but not at 6 months, lower epididymal fat weight (LL: 37.0 ± 1.62; LH: 34.1 ± 1.79; HL: 37.4 ± 2.27; HH: 29.7 ± 1.80; pup diet: 0.006), lower serum LPS (LL: 4.77 ± 0.41; LH: 4.08 ± 0.32; HL: 4.35 ± 0.35; HH: 2.56 ± 0.34; dam diet: 0.011; pup diet: 0.002), lower fasting glucose (LL: 13.1 ± 0.65 vs. HH: 10.7 ± 0.44; p<0.039), and similar glucose tolerance and insulin resistance. Conclusion Reduced fat accumulation due to high vitamin D post-weaning and lower systemic LPS concentrations with lifelong exposure may contribute to lower fasting glucose levels; a risk factor for diabetes. Funded by Banting and Best Diabetes Centre Novo Nordisk Studentship, Centrum Foundation Research Innovation Fund, Department of Nutritional Sciences, U of T