Transgenerational effects on the liver and pancreas resulting from maternal vitamin D restriction in mice

This study aimed to investigate the effects of maternal vitamin D restriction on carbohydrate metabolism and alterations in the pancreas and liver in the F1 and F2 generations. Therefore, we studied the first two generations of offspring (F1 and F2) of Swiss mice from mothers fed one of two diets: SC (standard chow) or VitD⁻ (vitamin D-deficient). Biometric, biochemical and molecular analyses were performed. The VitD-F1 mice had greater body mass (BM) than the SC-F1 mice. The BM changes were accompanied by increased insulin secretion. The VitD-F1 mice had a higher area under the curve in the oral glucose tolerance test and exhibited larger islet diameters than the SC-F1 mice. In addition, the VitD-F1 mice showed marked diffuse hepatic steatosis and higher expression of fatty acid synthase (FAS) protein than the SC animals in either generation or the ViD-F2 mice. Diet accounted for a greater fraction of the total variation for BM, fat pad mass and insulin secretion than generation. Both diet and generation contributed to the variation in steatosis in the liver, islet diameter and expression of FAS. However, interactions between diet and generation were observed only for insulin secretion, steatosis in the liver and FAS expression. In conclusion, these results provide compelling evidence that maternal vitamin D restriction affects the development of the offspring and leads to metabolic alterations accompanied by structural alterations in the liver and pancreas, especially in the F1 generation.