Impact of a Short-Term High Fat Diet Versus A Short-Term Low Fat Diet on Expression of the Key Intestinal Genes Involved in the Cholesterol and Fatty Acid Metabolism Pathways
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Change in duodenal mRNA expression of NPC1L1, ABCG5/8, MTP and FATP4.
研究概览
简要总结
Dietary fat has been shown to modulate cholesterol and fatty acids homeostasis and several lines of evidence suggest that this effect is associated with changes in the regulation of different genes at the intestine level involved in the cholesterol and fatty acid metabolism pathways. The present study will examine the impact of a short-term high fat diet versus a short-term low fat diet on expression of Niemann-Pick C1-like 1 (NPC1L1), adenosine triphosphate (ATP) binding cassette transporters (ABCG5/8), microsomal triglyceride transfer protein (MTP) and fatty acid transport protein-4 (FATP4), which have been shown to play a critical role in intestinal cholesterol absorption, chylomicron synthesis and dietary lipid absorption. Gene expression studies will be performed on duodenal biopsies. The primary hypothesis is that a short-term high fat diet will significantly decrease duodenal messenger ribonucleic acid (mRNA) levels of NPC1L1, ABCG5/8, MTP and FATP4 as compared with a short-term low fat diet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Males 18 to 50 years of age
- •Non-smoker
- •Body mass index between 20.0 and 30.0 kg/m2
- •Plasma LDL-cholesterol levels between the 25th and 75th percentile for their age at day -14
- •Plasma triglyceride levels < 1.7 mmol/L (150 mg/dl) at day -14
- •Plasma HDL-cholesterol levels between 0.9 (35 mg/dl) and 1.6 mmol/L (60 mg/dl) at day -14
- •Subjects must be willing to give written informed consent and able to adhere to the diet schedule and visit schedule
- •Patients should be otherwise healthy, without elevations in hepatic transaminases or creatine kinase (CK) or abnormal renal function or coagulation
排除标准
- •Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded
- •Subjects will be excluded if they have cardiovascular disease (CHD, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (eg. steroids, beta blockers, thiazide diuretics, other lipid lowering agents, significant alcohol intake etc.)
结局指标
主要结局
Change in duodenal mRNA expression of NPC1L1, ABCG5/8, MTP and FATP4.
时间窗: At the end of the two 3-days diets (day 3 and day 17).
Six biopsies (3 X 3 mm) will be obtained from the second portion of the duodenum during gastro-duodenoscopy. Biopsy specimen will be stored at -86°C before mRNA extraction. Total RNA will be isolated and used for polymerase chain reaction (PCR) quantification.
次要结局
- Change in surrogate markers of cholesterol absorption and synthesis.(At the end of the two 3-days diets (day 3 and day 17).)
研究者
Patrick Couture
MD, FRCP, PhD
Laval University