Effects of vitamin D supplementation on sirtuin-1, Angiogenesis fac-tors and Matrix metalloproteinases enzmes in Obese subjects with Vitamin D Insufficiency/ Deficiency

Abstract

Background and Objectiv: Obesity is one of the major public health problems that is caused by positive energy balance leading to enlargement of adipose tissue and results in hypoxia development and extracellular matrix accumulation (ECM). Cellular response to hypoxia is mediated by up-regulation many pro-angiogenesis factors, matrix metallo-proteinases enzymes and subsequently down–regulation anti-angiogenesis factors and sirtuins. There are increasing lines of evidence that vitamin D regulates hypoxia and angiogenesis. Therefore this study was aimed to assess the effect of sirtuin-1, angio-genesis factors and matrix metalloproteinases enzmes in obese subjects with vitamin D deficiency. Materials and methods: In this double-blind placebo-controlled randomized clinical trial, 44 obese subjects with vitamin D deficiency (25 (OH) vitamin D < 50 nmol/L) were randomly assigned into vitamin D (a weight reduction diet + bolus weekly dose of 50000 IU vitamin D) or placebo group (weight reduction diet + placebo weekly) for 12 weeks. Dietary intakes information, physical activity and sun exposure were assessed before, at the middle and after of the intervention. The anthropometric indices was col-lected in before and after of the intervention. Venus blood samples of participants were obtained after 12-14 hours fasting to determine serum levels of Sirtuin1(SIRT-1), hypoxia- inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), Angiopoietin-like4 (Angptl4), thrombospondin 1 (TSP-1) ,vascular endothelial growth factor receptor 1 (VEGFR-1), matrix metalloproteinases (MMP2, MMP9), 25(OH)D, Calcium, Parathyroid hormone (PTH), Phosporous, fasting serum glucose (FSG), serum insulin, homeostasis model assessment insulin resistance (HOMA-IR) and Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-c were assessed before and after in-tervention. Results: After 12 weeks, weight, Body mass index (BMI), waist to hip ratio (WHR), Fat mass (FM) and visceral fat showed significant decreases in both groups compared to baseline (P<0.001). The mean change in weight and FM were statistically significant between the groups (P<0.05). Serum 25(OH)D level increased significantly with a sim-ultaneous decrease in PTH in vitamin D group (P< 0.001); changes in serum 25(OH) D and PTH were significant between the two groups (P<0.05). Although significant in-crease in SIRT-1 was observed in both groups, no significant differences was observed between groups at end of the study. Among pro-angiogenesis biomarkers, only serum HIF-1α significantly decreased in the vitamin D group (P= 0.025). Between groups differences in HIF-1 (P= 0.005) and TSP-1(P= 0.016) level were significant by the end of the study. There was a reduction in the serum MMP-9 level in both groups (P<0.05) and the differences between two group was statistically significant (P= 0.011). FSG, TC, TG decreased significantly in both group and LDL-c decreased in vitamin D group (P<0.05) but the differences in glycemic markers and lipid profile were not statistically significant between two group. Furthermore, there were no significant changes in food intake, physical activity and sun exposure between groups at beginning, in the middle and the end of study. Conclusion: Vitamin D supplementation improved vitamin D status, weight loss and some angiogenesis biomarkers during weight reduction diet. It seems, serum 25 (OH) D levels as high as 75 nmol/L or higher is needed to influence other angiogenesis bi-omarkers.