The effect of maternal vitamin D deficiency during pregnancy on body fat and adipogenesis in rat offspring

Abstract

To evaluate the effects of maternal vitamin D deficiency on body fat and adipogenesis in offspring rats, and explore the potential mechanism, we constructed a vitamin D deficient rat model and performed metabolic activity evaluation, body fat monitoring, biochemical analysis, adipogenesis assay, methylation microarray and RNA-seq for their offspring rats. We found the weight of vitamin D deficient (VDD) offspring was gradually higher than that of control (CLT) offspring, and the difference was significant since 10 weeks old. When compared with CTL offspring, the 24 h heat production, peak blood glucose, adipose tissue volume and blood lipid indexes were significantly increased in VDD offspring at 14 weeks old. Moreover, a significant increase in proliferation rate and number of lipid droplets for pre-adipocytes was also observed in VDD offspring group. DNA methylation profiling showed that compared to CTL group, 608 promoters and 204 CpG islands were differentially methylated in the VDD group, involving 305 genes. When combined with the results of RNA-seq, 141 genes of the methylated genes were differentially expressed. In conclusion, vitamin D deficiency during pregnancy may promote the proliferation and differentiation of pre-adipocytes, which may be associated with methylation alterations of genes, ultimately leading to offspring obesity.

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

“…A later epigenome-wide DNA methylation study in Sprague-Dawley rats found that offspring of VDD dams exhibited differential methylation in adipose tissue at >800 loci linked to 305 genes (Wen et al 2018). Differential expression was detected at 141 of the differentially methylated genes, including two validated lipid metabolism genes, Vldlr and Hif1α.…”

“…Differential expression was detected at 141 of the differentially methylated genes, including two validated lipid metabolism genes, Vldlr and Hif1α. These epigenetic and transcriptional changes were linked to obesityand metabolic dysfunction-related phenotypes in the offspring (Wen et al 2018). A separate epigenome-wide DNA methylation study also in Sprague-Dawley rats reported that progeny of VDD dams exhibited differential methylation at ten genes in the kidney including gain of methylation at Pannexin-1, Panx1, which is abundantly expressed in heart, skeletal muscle and vasculature (Meems et al 2016).…”

Effects of Vitamin D Supplementation on General and Central Obesity: Results from 20 Randomized Controlled Trials Involving Apparently Healthy Populations

“…On the one hand, VDD increases parathyroid hormone levels and promotes a greater inflow of calcium (Ca) into adipocytes [11]. On the other hand, VDD might accelerate the differentiation of preadipocytes into adipocytes [12]. Both conditions could influence the obesity risk either directly (e.g., by increasing adipogenesis) or indirectly (by modulating inflammation, oxidative stress, metabolism and gene regulation) [13].…”

Renal developmental disturbances and their long-term consequences in female pups from vitamin D-deficient mothers: involved mechanisms

“…Wen et al demonstrated that Vit.D deficiency during pregnancy stimulates the proliferation and differentiation of pre-adipocytes, which may be associated with the alteration in the methylation of genes, such as Vldlr and Hif1α, leading to offspring obesity. 18 The higher water intake and urinary volume in the Vit.Danimals may be a consequence of increased ANGII levels, leading to central stimuli thirst. 19 The Vit.D-animals also exhibited a decrease in urinary osmolality.…”