The influence of dietary n-6 polyunsaturated fats on the inflammatory state of macrophages
department or school: Arts and Sciences, Irving K. Barber School of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Winkler, John McCauley
issued: 2019-07-23T07:00:00Z
issued: 2019
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Dietary n-6 polyunsaturated fatty acids (n-6 PUFA) like linoleic acid (LA) are linked to inflammatory diseases. It is believed that arachidonic acid (ARA), generated from LA is primarily responsible for such inflammation. However, studies show that dietary LA does not raise ARA in vivo and chronic disease patients often demonstrate low serum ARA. Thus, I hypothesized that LA, the parent n-6 PUFA causes inflammation independent of ARA. First, I show that adding LA activates RAW 264.7 macrophages (MФs) which demonstrates increased mitochondrial respiration, glucose uptake, cholesterol storage and reactive oxygen species (ROS) production compared to oleic acid (OA), a monounsaturated fatty acid (MUFA). Interestingly though, feeding a diet rich in LA (corn oil, CO; 54% LA) or OA (olive oil, OO; 54% OA) for six weeks in mice did not alter the inflammatory state of macrophages (PMФs). However, when I fed these diets to ELOVL5 +/- mice, which were deficient in an enzyme that allows the conversion of LA to ARA and therefore has higher LA, the accumulation of LA in PMФs demonstrated proinflammatory effects. Taken together, I conclude that LA accumulation in the short-term does not activate macrophages but long-term accumulation of LA mediated by congenital ELOVL deficiency does. In addition, feeding a MUFA diet did not counteract the activation of macrophages or higher LA levels in ELOVL5 ⁺/⁻ mice. Thus, I conclude that dietary MUFA cannot overcome a genetic deficiency of ELOVL5, indicating the critical role of this enzyme in maintaining PUFA levels in macrophages. Thus, my thesis clarifies the crucial role of ELOVL5 in the PUFA bioconversion pathway and its central importance in regulating the pro-inflammatory properties of n-6 PUFA. In the current milieu of high LA in our diet, activation of ELOVL5 and clearance of LA could be used as a therapeutic target against inflammation.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/71127
note: THE INFLUENCE OF DIETARY N-6 POLYUNSATURATED FATS ON THE INFLAMMATORY STATE OF MACROPHAGES by John McCauley Winkler B.Sc., Lakehead University, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Biochemistry and Molecular Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) July 2019 © John McCauley Winkler, 2019 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis/dissertation entitled: The influence of dietary n-6 polyunsaturated fats on the inflammatory state of macrophages submitted by John McCauley Winkler in partial fulfillment of the requirements for the degree of Master of Science Examining Committee: Dr. Sanjoy Ghosh, Irving K. Barber School of Arts and Sciences Supervisor Dr. John Klironomos, Barber School of Arts and Sciences Supervisory Committee Member Dr. Isaac Li, Barber School of Arts and Sciences Supervisory Committee Member Dr. Jonathan Little, Barber School of Arts and Sciences University Examiner iii Abstract Dietary n-6 polyunsaturated fatty acids (n-6 PUFA) like linoleic acid (LA) are linked to inflammatory diseases. It is believed that arachidonic acid (ARA), generated from LA is primarily responsible for such inflammation. However, studies show that dietary LA does not raise ARA in vivo and chronic disease patients often demonstrate low serum ARA. Thus, I hypothesized that LA, the parent n-6 PUFA causes inflammation independent of ARA. First, I show that adding LA activates RAW 264.7 macrophages (MФs) which demonstrates increased mitochondrial respiration, glucose uptake, cholesterol storage and reactive oxygen species (ROS) production compared to oleic acid (OA), a monounsaturated fatty acid (MUFA). Interestingly though, feeding a diet rich in LA (corn oil, CO; 54% LA) or OA (olive oil, OO; 54% OA) for six weeks in mice did not alter the inflammatory state of macrophages (PMФ…
has type: Thesis/Dissertation
date issued: 2019-09
is shown at: 10.14288/1.0380206
language: eng
degree discipline: Biochemistry and Molecular Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/71127