The Role of Arachidonic Acid Metabolites, From Patients With Metabolic Syndrome

June 20, 2016 updated by: Gracie Ong @ Gracie Ong Siok Yan, University of Malaya

The Role of Arachidonic Acid Metabolites, in the Lipid Droplets of Macrophages From Patients With Metabolic Syndrome

The purpose of this study is to determine whether an increase in lipid bodies in leukocytes will lead to an increase in eicosanoid production. The 2nd purpose is to determine if there is a significant correlation between lipid body formation and enhanced generation of both Lipoxygenase (LO) and COX derived eicosanoids. The 3rd purpose is, if lipid bodies are involved in arachidonic acid (AA) metabolism, then AA present in these lipid rich structure must be released by phospholipases and the free Arachidonic Acid (AA) must have access to the eicosanoid forming enzyme. The fourth objective is to determine the compartmentalisation of cPLA2 and MAP kinases including ERK1, ERK2, p85 and p38 are involved in AA liberation within lipid bodies.

Study Overview

Status

Unknown

Conditions

Detailed Description

Metabolic syndrome is a cluster of biochemical and physiological abnormalities associated with the development of cardiovascular disease and type 2 diabetes mellitus. The current study focused on type 2 Diabetes Mellitus(T2DM). T2DM is a chronic disease in which people have problems regulating their blood sugar. This disorder consists of an array of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance of insulin action, inadequate insulin secretion and excessive or inappropriate glucagon secretion. Insulin resistance results from a complex interplay between nutrient overload, systemic fatty acid excess, inflammation of the adipose tissue, endoplasmic reticulum and oxidative stress.

At the molecular lever, inflammatory cytokines, fatty acid derivatives such as ceramides, diacylglycerols and reactive oxygen species (ROS), activate several serine/threonine kinases, that have emerged as important negative regulators of insulin signaling. Because of their ability to directly oxidize DNA, protein and lipid damage, ROS are believed to play a key role in the metabolic syndrome and the possible development of T2DM. It is possible that ROS and oxidative stress, induced by elevations in glucose and possibly free fatty acid levels play a key role in causing insulin resistance, and beta cell dysfunction by their ability to activate stress sensitive signaling pathways.

Lipids as signaling intermediates encompass a vast range of molecules with distinct function. The characteristics includes, lipid bodies(LB) are sites for the production of inflammatory mediators and LB within inflammatory cells contain arachidonyl lipids which serve as precursors for eicosanoids. In addition, formation of LB within inflammatory macrophages was positively correlated with augmented increase in prostaglandin E2 (PGE2) in changes. LB also could function as a draining compartment to rapidly uptake and re-acetylate free arachidonic acid with the potentially detrimental outcomes for the host cell.

Macrophage from cells with lipid bodies involves complex and multi step mechanisms that depend on different signaling pathways regulating lipid influx, metabolism storage and mobilization. In view of these clues the investigators have reason to believe that organic anion transporters might be resident or upon stimulation trans located to lipid bodies in order to export the newly synthesized lipid mediators into the cytoplasmic space. Once outside the lipid bodies the eicosanoids can exert intracrine functions or be exported to plasma membrane resident transporters to the extracellular space. Free fatty acids have adverse effects on the mitochondrial function including uncoupling of oxidative phosphorylation and the generation of ROS. Beta cell lipotoxicity has an amplifying effect only if mediated by concurrent hyperglycemia. The association of obesity, fatty acids and oxidative stress with insulin action clearly merits further attention with particular focus on the molecular mechanism.

Study Type

Observational

Enrollment (Anticipated)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Malaysia
    • Kuala Lumpur
      • Petaling Jaya, Kuala Lumpur, Malaysia, 50603
        • Recruiting
        • University Malaya Medical Center (UMMC)
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study subjects are recruited from Primary Care Clinic of University Malaya Medical Center

Description

Inclusion Criteria:

  • age ≥ 18 to ≤ 60
  • Patient diagnosed with Type 2 Diabetes Mellitus within 1 year

Exclusion Criteria:

  • Patients < 18 years
  • Patients with uncontrolled diabetes, heart failure and sepsis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Normal
Patient sample within the normal range of blood results.
Abnormal
Patient sample from freshly diagnosed Type 2 Diabetes Mellitus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite measure of patient physical observations to include weight, height and BMI
Time Frame: six months only (1 time only)
six months only (1 time only)

Secondary Outcome Measures

Outcome Measure
Time Frame
Reduction of pro - inflammatory cytokines
Time Frame: one year
one year
The effect of eicosanoids in diabetic complication
Time Frame: One year
One year
The effect of LTB4 and LTC4 of eicosanoids
Time Frame: One year
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Malaya

Investigators

  • Principal Investigator: Gracie Ong Siok Yan, Senior Consultant

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

January 1, 2016

Study Completion (Anticipated)

September 1, 2016

Study Registration Dates

First Submitted

May 14, 2015

First Submitted That Met QC Criteria

July 10, 2015

First Posted (Estimate)

July 15, 2015

Study Record Updates

Last Update Posted (Estimate)

June 21, 2016

Last Update Submitted That Met QC Criteria

June 20, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG291-14AFR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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