Dietary Sources of Lysophospholipids

Sponsor

Susan Smyth (Other)

Overall Status

Terminated

CT.gov ID

NCT02952638

Collaborator

(none)

Enrollment

Location

4.6

Actual Duration (Months)

9.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to test the hypothesis that dietary intake of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) acutely alters plasma lysophosphatidic acid (LPA) levels and autotaxin activity in normal weight and obese subjects.

Condition or Disease	Intervention/Treatment	Phase
Obesity Cardiovascular Risk Factor Hyperlipidemia

Detailed Description

Lysophosphatidic acid (LPA) is a simple glycerophospholipid that is found at biologically-relevant levels in plasma and has important effects on isolated or cultured blood, vascular and fat cells. The main enzyme responsible for generation of plasma LPA is the secreted lysophospholipase D, autotaxin (ATX). Adipocytes contribute substantially to plasma ATX levels. The investigators have demonstrated rapid production and metabolism of plasma LPA in animals. More recently, the investigators have observed that plasma LPA levels increase in mice fed a high fat ("Western") diet in comparison to levels found in mice fed normal chow. The investigators have also found that diet-induced obesity increased circulating ATX levels in mice. The investigators hypothesize that diet, and in particular dietary phosphatidylcholine (PC), may regulate the autotaxin substrate lysophosphatidylcholine (LPC), from which LPA is derived. Obesity may amplify the response by increasing plasma ATX levels and/or activity. The current study will test whether dietary PC in normal weight and obese subjects acutely alters LPA levels and autotaxin activity.

Study Design

Study Type:

Observational

Actual Enrollment :

44 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Dietary Sources of Lysophospholipids

Actual Study Start Date :

Jul 14, 2015

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Healthy BMI is between 20 and 25
Overweight BMI is between 25 and 30
Obese BMI is between 30 and 40

Outcome Measures

Primary Outcome Measures

Plasma Autotaxin-dependent formation of Lysophosphatidic acid, and Levels of Phosphatidylcholine and its metabolites - Lysophosphatidylcholine, Lysophosphatidic acid, Choline, Trimethylamine and Trimethylamine oxide measured by Tandem Mass Spectrometry [8 hours]
Investigators will use tandem mass spectrometry to measure the most abundant metabolite species. Enzymatic activity of autotaxin involves incubation with the substrate lysophosphatidylcholine and monitoring concentration dependent release of lysophosphatidic acid. Levels of Lysophospholipids Phosphatidylcholine and the products of its metabolism in the blood will be measured. Quantitation will be achieved by stable isotope dilution and by reference to offline calibration curves. By using mass spectrometry and metabolic tracers, studies using a common protocol are effectively multiplexed so data on both endogenous and mass labeled lipids can be obtained from a single individual. Given the sensitivity of these analytical methods (limits of quantitation of approximately 1 fmol), the measurements and the quantities will be reported as concentration in picomoles per liter of plasma volume. A statistical correlation with each group based on BMI will be performed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 18 to 60 years old
Body Mass Index of 20 and above
Must be able to consume a low fat meal, unlimited fruits and vegetables and not eating after midnight the night before the lipid tolerance test
Report to the clinical research unit fasting (no food since the meal the night before)
Able to consume a liquid meal consisting of a commercial nutritional product supplemented with fat
Able to have an indwelling catheter placed on one arm and have hourly blood draws for 8 hours