Impact of a Short-Term High Fat or Low Fat Diet on Intestinal Genes Expression Involved in the Cholesterol and Fatty Acid Metabolism

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

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.)