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

NCT01806441 | Completed

• 1 other identifier: INAF-125-05-06
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gene Expression

Outcome Measures

Primary Outcomes (1)

• Change in duodenal mRNA expression of NPC1L1, ABCG5/8, MTP and FATP4.

  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.

  At the end of the two 3-days diets (day 3 and day 17).

Secondary Outcomes (1)

• Change in surrogate markers of cholesterol absorption and synthesis.

  At the end of the two 3-days diets (day 3 and day 17).

Study Arms (2)

3-days high fat diet

EXPERIMENTAL

During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).

Other: 3-days high fat diet

3-days low fat diet

ACTIVE COMPARATOR

During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).

Other: 3-days low fat diet

Interventions

3-days high fat diet OTHER

During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).

3-days high fat diet

3-days low fat diet OTHER

During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).

3-days low fat diet

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

Institute of nutrition and functional food

Québec, Quebec, G1V 0A6, Canada

Location

Related Publications (1)

• Tremblay AJ, Lamarche B, Guay V, Charest A, Lemelin V, Couture P. Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men. Am J Clin Nutr. 2013 Jul;98(1):32-41. doi: 10.3945/ajcn.113.060251. Epub 2013 May 29.

  PMID: 23719552 DERIVED

MeSH Terms

Interventions

Diet, High-Fat; Diet, Fat-Restricted

Intervention Hierarchy (Ancestors)

Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet Therapy; Nutrition Therapy; Therapeutics

Study Officials

• Patrick Couture, MD,FRCP,PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FRCP, PhD

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 7, 2013
• Study Start: February 1, 2009
• Primary Completion: May 1, 2009
• Study Completion: December 1, 2010
• Last Updated: March 7, 2013

Record last verified: 2013-03

Locations

CA (1)