Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran -
Minerva Med. 2014 Feb;105(1):63-78.
Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR), PPARγ and PGC1α gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo.
A total of 94 obese participants (BMI≥30) were recruited for the current double blind clinical trial study. Patients were divided into two intervention (N.=40) and control groups (N.=54) based on the stratified randomized method. One-Alpha® Capsules 1 microgram: alfacalcidol (1-α hydroxyvitamin D3) and placebo were given to subjects once a day for 8 weeks. Analysis of body composition was performed with use of Body Composition Analyzer. The circulating levels of TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured with the use of EIA method. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. The real-time PCR using specific primer pairs for VDR, PGC1α, PPARγ, and β-actin was performed.
The FPG, fat percent and PTH levels were decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were significantly increased after treatment with Alfacalcidol. Regarding to cytokines levels, the levels of IL6 were significantly decreased and IL10 were significantly increased in Alfacalcidol group in comparison with the control group. The relative expressions of VDR, PGC1α, and PPARγ genes significantly increased in Alfacalcidol group. We found also significant positive correlation between circulating 25-OH vitamin D and relative PGC1α gene expression in participants with insulin resistance.
It seems that Alfacalcidol treatment may be effective in amelioration of the inflammatory state in obesity. This supplement might also improve resistance to insulin through enhancement of relative VDR and its downstream genes expression, which are demonstrated to be involved in glucose homeostasis pathways.
肥胖引起的慢性炎症是胰岛素抵抗发病机制的一个关键组成部分。越来越多的证据表明维生素 D 具有抗炎特性。尽管维生素 D3 的类似物已广泛用于治疗各种慢性炎症性疾病，但据我们所知，尚未对肥胖症进行此类研究。本双盲临床试验旨在研究在肥胖受试者中使用阿尔法骨化醇治疗是否会影响细胞因子谱和胰岛素抵抗。此外，我们评估了维生素 D 受体 (VDR)、过氧化物酶体增殖物激活受体 γ (PPARγ) 和过氧化物酶体增殖物激活受体 γ 辅激活因子 1α (PGC1α) 基因表达的途径，这些途径可能导致用阿尔法骨化醇或安慰剂治疗后出现胰岛素抵抗。
共有 94 名肥胖参与者（BMI≥30）被纳入本双盲临床试验研究。根据分层随机方法，将患者分为两组干预组（N=40）和对照组（N=54）。每天给受试者服用 1 微克的 One-Alpha®胶囊 1 微克：阿尔法骨化醇（1-α 羟基维生素 D3）和安慰剂，持续 8 周。使用身体成分分析仪进行身体成分分析。使用 EIA 法测量 TNF-α、IL-1β、IL-4、IL-6、IL-10、IL-13、IL-17、PTH 和 25-羟基维生素 D 的循环水平。使用菲可法从全血中分离 PBMCs。提取总细胞 RNA 并合成 cDNA。使用针对 VDR、PGC1α、PPARγ 和 β-肌动蛋白的特异性引物对进行实时 PCR。
治疗后，空腹血糖（FPG）、脂肪百分比和 PTH 水平降低，HDL-胆固醇和 25-羟维生素 D 水平显著升高。关于细胞因子水平，与对照组相比，IL6 水平显著降低，IL10 水平显著升高。阿尔法骨化醇组 VDR、PGC1α 和 PPARγ 基因的相对表达显著增加。我们还发现，在胰岛素抵抗患者中，循环 25-OH 维生素 D 与相对 PGC1α 基因表达之间存在显著正相关。
阿尔法骨化醇治疗似乎可有效改善肥胖症中的炎症状态。这种补充剂还可能通过增强参与葡萄糖稳态途径的相对 VDR 及其下游基因表达来改善胰岛素抵抗。
