Transgenerational Effects on the Liver and Pancreas Resulting from Maternal Vitamin D Restriction in Mice

Abstract

SummaryThis 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 2 (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.

Prenatal maternal vitamin D deficiency sex‐dependently programs adipose tissue metabolism and energy homeostasis in offspring

“…Interestingly, in males submitted to HF diet, we observed higher insulin plasma level, glycemia, HOMA IR and insulin resistance, as previously reported in control conditions. 24,[32][33][34] Surprisingly, in females, no perturbation of the glucose homeostasis was observed. At the opposite, VDD-HF females displayed similar values as CTRL-LF or VDD-LF for several parameters, including insulinemia, glycemia, and HOMA-IR.…”

Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

“…In one of the earliest transgenerational mouse vitamin D fetal programming studies, compared with controls, 6-month-old F1 generation offspring of VDD dams displayed greater body and epididymal fat mass (Nascimento et al 2013). These mice also had increased insulin secretion when given an oral glucose challenge and showed marked hepatic steatosis.…”

Transgenerational effects of maternal diet on metabolic and reproductive ageing

“…More recently, it has been shown that a grand-maternal (F0) high-fat diet in the mouse has the opposite effect, with an increase in pancreatic mass and islet density persisting to the F2 generation (Graus-Nunes et al 2015 ). In a mouse model of grand-maternal vitamin D deficiency, not only the size of pancreatic islets, but also the amount of steatosis present in the liver of the F2 generation was affected by the transgenerational exposure (Nascimento et al 2013 ). However, in order to have a direct effect on the structure and function of organs in the F2 generation, it is not sufficient for the F1 generation merely to have structural alterations in organs such as the pancreas and liver.…”