Correlation of Serum Vitamin D, Adipose Tissue Vitamin D Receptor, and Peroxisome Proliferator-Activated Receptor Gamma in Women with Gestational Diabetes Mellitus
Gestational diabetes mellitus (GDM) is a common complication during pregnancy, characterized by the onset of diabetes-associated symptoms in women who previously had normal glucose metabolism. The incidence of GDM in China has been on the rise, reaching 17.5% according to recent statistics. GDM poses significant risks to both maternal and child health, increasing the likelihood of metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular diseases in affected women. Additionally, GDM is associated with higher rates of cesarean deliveries, higher birth weights in newborns, and increased risks of depression and impaired glucose tolerance in childhood.
The pathogenesis of GDM is multifactorial, with insulin resistance (IR) and decreased islet beta cell secretion being key contributors. Obesity and overweight status are closely linked to metabolic diseases and diabetes, and recent research suggests that adipose tissue plays a critical role in the development of GDM. Vitamin D (VD) has also been implicated in GDM, with low VD levels being associated with an increased risk of the condition. This study aimed to investigate the correlation between serum VD levels, VD receptor (VDR) expression, and peroxisome proliferator-activated receptor gamma (PPARg) expression in the adipose tissue of overweight or obese women with GDM.
The study included 140 pregnant women who underwent full-term single-birth cesarean sections. The participants were divided into four groups: 70 women with GDM (35 non-overweight/non-obese [G1] and 35 overweight/obese [G2]) and 70 women with normal glucose tolerance (35 non-overweight/non-obese [N1] and 35 overweight/obese [N2]). Serum VD levels, blood biochemistry, and adiponectin levels were measured in all participants. Subcutaneous adipose tissue was collected from the abdominal wall incision during cesarean section, and the expression levels of VDR and PPARg messenger RNA (mRNA) were quantified using real-time polymerase chain reaction (PCR). Western blotting was used to detect the differences in PPARg protein levels and the degree of PPARg Ser273 phosphorylation.
The results revealed that serum VD levels were significantly lower in women with GDM compared to those with normal glucose tolerance. The lowest VD levels were observed in overweight/obese women with GDM. Conversely, the expression of VDR and PPARg mRNA in adipose tissue was higher in women with GDM compared to those with normal glucose tolerance, with the highest expression levels observed in overweight/obese women with GDM. VDR mRNA levels were positively correlated with pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARg mRNA levels. In contrast, VDR mRNA levels were negatively correlated with serum VD and adiponectin levels. Similarly, PPARg mRNA levels were positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid (FFA), and VDR mRNA levels, while negatively correlated with serum VD and adiponectin levels.
The study also found that the degree of PPARg Ser273 phosphorylation was increased in obese and GDM pregnant women. Immunohistochemistry confirmed that VDR and PPARg were expressed in the nuclei of adipocytes, with higher expression levels observed in GDM women compared to those with normal glucose tolerance. Quantitative PCR analysis further supported these findings, showing that VDR and PPARg mRNA levels were significantly higher in GDM women, particularly in those who were overweight or obese.
The findings suggest that both GDM and overweight/obese women exhibit decreased serum VD levels and up-regulated VDR and PPARg mRNA expression in adipose tissue. These changes are more pronounced in overweight or obese women with GDM. The study proposes that VD may regulate the formation and differentiation of adipocytes through the VDR and PPARg pathways, thereby participating in the development of GDM.
The study’s results align with previous research indicating that obesity and low VD status are closely related to GDM. Obesity is associated with impaired VD metabolism, as adipocytes can inhibit the expression of enzymes involved in VD synthesis, such as 25-hydroxylase (CYP2J2) and 1α-hydroxylase (CYP27B1). Additionally, adipose tissue can act as a reservoir for VD, limiting its biological activity. On the other hand, VD, through its receptor VDR, can influence adipocyte formation and cytokine secretion, further linking VD status to adipose tissue function.
PPARg, a nuclear transcription factor abundant in adipose tissue, plays a crucial role in adipocyte production and fatty acid metabolism. It is closely associated with metabolic syndrome and is necessary for lipid formation both in vivo and in vitro. The study found that PPARg expression was significantly higher in GDM women, particularly in those who were overweight or obese. This suggests that PPARg may be involved in the dysregulation of lipid metabolism observed in GDM.
The study also highlighted the role of adiponectin, an adipokine that acts as an endogenous insulin sensitizer. Lower levels of adiponectin were observed in GDM women, particularly in those who were overweight or obese. Adiponectin is known to up-regulate PPARg expression, and its decreased levels in obesity and diabetes may contribute to insulin resistance and beta cell dysfunction.
The findings of this study have important implications for the prevention and management of GDM. The results suggest that maintaining adequate VD levels and managing body weight during pregnancy may help reduce the risk of GDM. Additionally, targeting the VDR and PPARg pathways could offer new therapeutic strategies for the treatment of GDM and associated metabolic disorders.
In conclusion, this study provides evidence that serum VD levels, VDR expression, and PPARg expression in adipose tissue are closely related to the development of GDM, particularly in overweight or obese women. The findings suggest that VD, through its interaction with VDR and PPARg, plays a role in the regulation of adipocyte formation and differentiation, contributing to the pathogenesis of GDM. Further research is needed to explore the molecular mechanisms underlying these interactions and to develop targeted interventions for the prevention and treatment of GDM.
doi.org/10.1097/CM9.0000000000000480
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