Determining the Responsiveness of Intestinal Lipoprotein Production to an Elevation of Plasma Free Fatty Acids

• Status: Completed
• Trial end date: 2008-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Lipoproteins are large complexes of molecules that transport lipids (primarily triglycerides and cholesterol) through the blood. The intestine has traditionally been viewed as a 'passive' organ with respect to lipoprotein production, with intestinal lipoprotein production rates responding mainly to fat ingestion and absorption. The investigators have recently demonstrated in animal models that there is an overproduction of intestinal lipoproteins in both the fasted and the fed state. The investigators have also recently demonstrated that an elevation of plasma free fatty acids (FFAs) stimulates intestinal lipoprotein in hamsters. It is not known whether intestinal lipoprotein production can be acutely stimulated by an elevation of plasma FFAs in humans.

Hypothesis: Intestinal lipoprotein particle production in humans can be stimulated by an acute elevation of plasma free fatty acids.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Glycerol; Soybean oil, phospholipid emulsion

Criteria

Inclusion Criteria:

1. Non-diabetic men and women aged 18-65 years old

2. Written informed consent obtained

3. Body mass index (BMI) < 27 kg/m2

4. Fasting triglycerides < 2.5 mmol/l

5. Waist circumference < 90 cm

6. Fasting blood glucose < 6 mmol/l

7. Haemoglobin above 130 g/L.

Exclusion Criteria:

1. Patient has a history of hepatitis/hepatic disease that has been active within the previous 2 years.

2. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (creatinine [Cr] > 1.5 mg/dL) genitourinary, or hematological systems; or severe uncontrolled treated or untreated hypertension (sitting diastolic blood pressure [BP] > 100 or systolic > 180); or proliferative retinopathy.

3. Fasting blood glucose > 6 mmol/l or known diabetes.

4. Any history of a myocardial infarction (MI) or clinically significant, active, cardiovascular history including a history of arrhythmias or conduction delays on electrocardiogram (ECG), unstable angina, or decompensated heart failure.

5. Any laboratory values: AST > 2x upper limit of normal (ULN); ALT > 2x ULN; thyroid-stimulating hormone (TSH) > 6 mU/l.

6. Known or suspected allergy to the medication or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.

7. Current addiction to alcohol or substances of abuse as determined by the investigator.

8. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation

9. Any lipid lowering or hypoglycemic agents

10. Will not donate blood three months before start or three months after completing study.

11. Thrombocytopenia