Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase. Primary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance. Secondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
Laval University
Québec, Quebec, Canada
Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation). We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation). We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation). We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation). We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
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