Assessing the Effects of Alfacalcidol Intake on Expression of Involed Gene in Metabolism in Obese Subjects

• Expression of VDR, PPARγ and PGC1α gene [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]
  measurement of Relative gene expression with RT-PCR.
  
  

• Change of weight [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]
  measurement with Body composition device
  
  

• Body mass index change [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]
  calculated with BMI equation
  
  

Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. The anti-inflammatory characteristics of vitamin D have been demonstrated in previous studies. In addition to its role in bone and calcium metabolism, vitamin D is demonstrated to be influential in the regulation of different immune system functions and glucose homeostasis pathways. Although low levels of vitamin D have shown to be in close correlation with obesity, whether vitamin D deficiency is the cause or the consequence of obesity remains unclear. It is noteworthy that several studies have demonstrated that vitamin D deficiency is associated with an increased resistance to insulin.

The biologic effects of vitamin D are primarily mediated via the nuclear transcription factor, vitamin D receptor (VDR), which triggers the expression of vitamin D responsive genes. VDR is expressed on different immune cells such as monocytes, T-lymphocytes, and granulocytes. It is documented that VDR and PGC-1α show an overlapping pattern of expression. Furthermore, as the expression of PGC-1α and PPARγ are regulated via environmental stimuli such as diet, it could be suggested that the function of VDR function can also be altered in response to external stimuli. PGC-1α was demonstrated to be of a particular importance in amelioration of increased insulin sensitivity.

Accordingly, to evaluate whether alphacalcidol treatment in obese subjects who generally suffer from a low state chronic inflammation could affect the insulin resistance, we designed the current double blind clinical trial study to compare the effect of alfacalcidol with placebo on serum glucose, 25-OH vitamin D, PTH, and lipid profile levels as well as Homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) indexes as a markers of insulin resistance. Furthermore, to assess the possible cross talk between VDR and PPARγ, the gene expressions of these VDR, PPARγ and PGC1α were evaluated following a course of treatment with either alphacalcidol or placebo.