The Effect of Dietary Lauric Acid on the Production of the LRH-1 Ligand, Dilauroylphosphatidylcholine

Study Overview
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Brief Summary
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A phosphatidylcholine species enriched with lauric acid at both the sn-1 and sn-2 positions, dilauroylphosphatidylcholine (DLPC), was recently identified as a ligand for the nuclear receptor, liver receptor homolog-1 (LRH-1). To date, DLPC has not been reported in vitro or in vivo, and has yet to be catalogued in the human metabolomics database. This intervention trial aims to determine the impact of consumption of dietary lauric acid, in the form of coconut oil (49% lauric acid), can facilitate the production of DLPC in humans.

Detailed Description
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A phosphatidylcholine species enriched with lauric acid at both the sn-1 and sn-2 positions, dilauroylphosphatidylcholine (DLPC), was recently identified as a ligand for the nuclear receptor, liver receptor homolog-1 (LRH-1). LRH-1 has notable roles in regulating sterol metabolism, with downstream impacts on reproductive capacity, bile acid production, glucose metabolism, and cell proliferation. Manipulation of LRH-1 activity via ligand-inducing binding and activation has the potential to act as a therapy in certain metabolic disorders, such as type 2 diabetes. To date, the LRH-1 ligand, DLPC, has not been reported in vitro or in vivo, and has yet to be indexed in the Human Metabolomics Database, suggesting that it's therapeutic potential is limited to pharmacological administration. The investigators' forthcoming unpublished research tested the hypothesis that the lack of DLPC in physiological systems results from substrate insufficiency, and have observed that consumption of dietary lauric acid facilitates the production of DLPC in animal models, and addition of lauric acid to the culture media of cells additionally leads to its production. A single acute gavage of coconut oil results in the production of DLPC in the intestine and export in the serum 1-2 hours post-gavage. To extend this work to humans, the investigators are undertaking an acute, randomized, cross-over trial of dietary lauric acid consumption. This intervention trial aims to determine whether dietary lauric acid, in the form of coconut oil (49% lauric acid), can facilitate the production of DLPC in humans. The investigators have hypothesized that consumption of a single breakfast shake containing coconut oil will result in DLPC in post-prandial serum. Participants will be invited to the Cornell University Human Metabolic Research Unit (HMRU) on 2 separate occasions to consume 1 of 2 breakfast shake , delivered in random order. Shakes will be made with either 2 tablespoons of olive oil (control) or coconut oil (intervention). Participants will arrive to the HMRU fasted and provide a baseline blood sample, prior to consumption of the breakfast shake ; at 2, 4, and 6 hours following the meal, participants will provide additional blood samples. Prior to and throughout the duration of the study, participants will be asked to avoid consumption of tropical oils. Lauric acid is typically a minimal component of the common diet, though substantial intakes can occur with the consumption of tropical oils, such as coconut oil or palm kernel oil. Lauric acid is considered one of the three primary hypercholesterolemic saturated fatty acids and is currently not recommended to constitute a major component of the diet; participants for whom a cholesterol lowering diet is recommended will not be able to enroll in the study.

Official Title
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Production of a LRH-1 Ligand in Humans: A Randomized,Controlled, Cross-Over Feeding Trial

Conditions
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Diet Modification

Intervention / Treatment
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* Other: Lauric acid (coconut oil)
* Other: No Lauric acid (olive oil)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness to comply with the study protocol Ability to overnight fast Willingness to donate blood 'generally healthy' Exclusion Criteria: self-reported regular consumption of tropical oils or supplements containing lauric acid self-reported food allergies to shake ingredients medical conditions where blood draws or fasting may be contraindicated major gastrointestinal conditions, such as inflammatory bowel disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Acute feeding study. Participants will arrive at our Human Metabolic Research Unit on 2 separate occasions. Participants will be randomized to consume 1 of 2 shake on each occasion. Shakes will be prepared with 2 tablespoons of either control (olive) or intervention (coconut) oils.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Olive Oil Shake<br>Intervention: No Lauric Acid A breakfast shake made from a complete meal shake will be prepared with water and supplemented with 2 tablespoons of olive oil. | Other: No Lauric acid (olive oil)<br>* A breakfast shake made from a complete meal shake will be prepared with water and supplemented with 2 tablespoons of olive oil.<br>|
| Experimental: Coconut Oil Shake<br>Intervention: Lauric Acid A breakfast shake made from a complete meal shake will be prepared with water and supplemented with 2 tablespoons of coconut oil. | Other: Lauric acid (coconut oil)<br>* A breakfast shake made from a complete meal shake will be prepared with water and supplemented with 2 tablespoons of coconut oil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLPC in Postprandial Serum | The presence of DLPC in postprandial serum will be measured using Liquid Chromatography Tandem Mass Spectrometry | 6 hours postprandial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Total Bile Acids | Serum total bile acids may be measured following shake consumption using a colorimetric assay. | 6 hours postprandial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatty acid, nutrition, metabolism, lauric acid, dilauroylphosphatidylcholine, lrh-1