Differential Effects of Saturated and Polyunsaturated Fatty Acids on Chylomicron Secretion and Expression of Key Genes and Proteins That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With Insulin-resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in TRL apolipoprotein B48 (apoB-48) production rate.
研究概览
简要总结
The overaccumulation of apolipoprotein (apo)B-48-containing lipoproteins of intestinal origin observed in patients with insulin-resistance is now thought to be attributable to both elevated intestinal production and reduced clearance of these lipoproteins. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease (CVD) risk. Therefore, reduction of atherogenic plasma TRL levels of intestinal origin appears to be crucial to improve CVD risk associated with insulin-resistance. In this regard, there is some evidence that the clinical recommendation to replace dietary saturated fatty acids (SFAs) by n-6 polyunsaturated fatty acids (PUFAs) reduces CVD risk in the general population. Although the beneficial impact of n-6 PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic n-6 PUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia. The impact of substituting SFAs by n-6 PUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal triglyceride-rich lipoproteins (TRLs) represent a large proportion of the atherogenic lipoproteins. The general objective of the proposed research is to investigate how dietary n-6 PUFAs in place of SFAs modify intestinal lipoprotein metabolism in men with dyslipidemia associated with insulin-resistance. The investigators hypothesize that the intestinal secretion of apoB-48-containing lipoproteins will be lower following a diet rich in n-6 PUFAs than after consuming a diet rich in SFAs. The investigators also hypothesize that substitution of SFAs by n-6 PUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.
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 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men aged between 18-60 years
- •Waist circumference > 102 cm
- •HDL-cholesterol < 1.1 mmol/L
- •Triglycerides > 1.7 mmol/L
- •Fasting blood glucose > 6.1 mmol/L
- •Normal blood pressure (<130/85)
排除标准
- •Men < 18 or > 60 years
- •Smokers (> 1 cigarette/day)
- •Body weight variation > 10% during the last 6 months prior to the study baseline
- •Subjects with a previous history of cardiovascular disease
- •Subjects with type 2 diabetes
- •Subjects with a monogenic dyslipidemia
- •Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
- •Subjects with endocrine or gastrointestinal disorders
- •History of alcohol or drug abuse within the past 2 years
- •Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
结局指标
主要结局
Change in TRL apolipoprotein B48 (apoB-48) production rate.
时间窗: At week 4 and week 12 (at the end of the two 4-weeks diets).
次要结局
- Changes in duodenal expression of genes that regulate intestinal lipid synthesis.(At week 4 and week 12 (at the end of the two 4-weeks diets).)
- Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).(At week 4 and week 12 (at the end of the two 4-weeks diets).)
- Changes in duodenal expression of genes that regulate intestinal lipid absorption.(At week 4 and week 12 (at the end of the two 4-weeks diets).)
研究者
Patrick Couture
MD, FRCP, PhD
Laval University