The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules

In this study, we aimed to identify the mechanisms underlying the different effects of palmitic acid and oleic acid on human pancreatic beta cell function. To address this problem, the oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis and their mediator molecules have been inve...

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Main Authors: Miruna Nemecz, Alina Constantin, Madalina Dumitrescu, Nicoleta Alexandru, Alexandru Filippi, Gabriela Tanko, Adriana Georgescu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.01554/full
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author Miruna Nemecz
Alina Constantin
Madalina Dumitrescu
Nicoleta Alexandru
Alexandru Filippi
Gabriela Tanko
Adriana Georgescu
author_facet Miruna Nemecz
Alina Constantin
Madalina Dumitrescu
Nicoleta Alexandru
Alexandru Filippi
Gabriela Tanko
Adriana Georgescu
author_sort Miruna Nemecz
collection DOAJ
description In this study, we aimed to identify the mechanisms underlying the different effects of palmitic acid and oleic acid on human pancreatic beta cell function. To address this problem, the oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis and their mediator molecules have been investigated in the insulin releasing beta cells exposed to palmitic and/or oleic acid. Herein, we have demonstrated that in cultured 1.1B4 beta cells oleic acid promotes neutral lipid accumulation and insulin secretion, whereas palmitic acid is poorly incorporated into triglyceride and it does not stimulate insulin secretion from human pancreatic islets at physiologically glucose concentrations. In addition, palmitic acid caused: (1) oxidative stress through a mechanism involving increases in ROS production and MMP-2 protein expression/gelatinolytic activity associated with down-regulation of SOD2 protein; (2) endoplasmic reticulum stress by up-regulation of chaperone BiP protein and unfolded protein response (UPR) transcription factors (eIF2α, ATF6, XBP1u proteins) and by PTP-1B down-regulation in both mRNA and protein levels; (3) inflammation through enhanced synthesis of proinflammatory cytokines (IL6, IL8 proteins); and (4) apoptosis by enforced proteic expression of CHOP multifunctional transcription factor. Oleic acid alone had opposite effects due to its different capacity of controlling these metabolic pathways, in particular by reduction of the ROS levels and MMP-2 activity, down-regulation of BiP, eIF2α, ATF6, XBP1u, CHOP, IL6, IL8 and by SOD2 and PTP-1B overexpression. The supplementation of saturated palmitic acid with the monounsaturated oleic acid reversed the negative effects of palmitic acid alone regulating insulin secretion from pancreatic beta cells through ROS, MMP-2, ATF6, XBP1u, IL8 reduction and SOD2, PTP-1B activation. Our findings have shown the protective action of oleic acid against palmitic acid on beta cell lipotoxicity through promotion of triglyceride accumulation and insulin secretion and regulation of some effector molecules involved in oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis.
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spelling doaj.art-81da2393c32f4b46a9b20f40a2cea8d92022-12-22T01:48:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-01-01910.3389/fphar.2018.01554416235The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector MoleculesMiruna NemeczAlina ConstantinMadalina DumitrescuNicoleta AlexandruAlexandru FilippiGabriela TankoAdriana GeorgescuIn this study, we aimed to identify the mechanisms underlying the different effects of palmitic acid and oleic acid on human pancreatic beta cell function. To address this problem, the oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis and their mediator molecules have been investigated in the insulin releasing beta cells exposed to palmitic and/or oleic acid. Herein, we have demonstrated that in cultured 1.1B4 beta cells oleic acid promotes neutral lipid accumulation and insulin secretion, whereas palmitic acid is poorly incorporated into triglyceride and it does not stimulate insulin secretion from human pancreatic islets at physiologically glucose concentrations. In addition, palmitic acid caused: (1) oxidative stress through a mechanism involving increases in ROS production and MMP-2 protein expression/gelatinolytic activity associated with down-regulation of SOD2 protein; (2) endoplasmic reticulum stress by up-regulation of chaperone BiP protein and unfolded protein response (UPR) transcription factors (eIF2α, ATF6, XBP1u proteins) and by PTP-1B down-regulation in both mRNA and protein levels; (3) inflammation through enhanced synthesis of proinflammatory cytokines (IL6, IL8 proteins); and (4) apoptosis by enforced proteic expression of CHOP multifunctional transcription factor. Oleic acid alone had opposite effects due to its different capacity of controlling these metabolic pathways, in particular by reduction of the ROS levels and MMP-2 activity, down-regulation of BiP, eIF2α, ATF6, XBP1u, CHOP, IL6, IL8 and by SOD2 and PTP-1B overexpression. The supplementation of saturated palmitic acid with the monounsaturated oleic acid reversed the negative effects of palmitic acid alone regulating insulin secretion from pancreatic beta cells through ROS, MMP-2, ATF6, XBP1u, IL8 reduction and SOD2, PTP-1B activation. Our findings have shown the protective action of oleic acid against palmitic acid on beta cell lipotoxicity through promotion of triglyceride accumulation and insulin secretion and regulation of some effector molecules involved in oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis.https://www.frontiersin.org/article/10.3389/fphar.2018.01554/fullpalmitic acidoleic acidhuman pancreatic beta cellsendoplasmic reticulum stressinflammationoxidative stress
spellingShingle Miruna Nemecz
Alina Constantin
Madalina Dumitrescu
Nicoleta Alexandru
Alexandru Filippi
Gabriela Tanko
Adriana Georgescu
The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
Frontiers in Pharmacology
palmitic acid
oleic acid
human pancreatic beta cells
endoplasmic reticulum stress
inflammation
oxidative stress
title The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
title_full The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
title_fullStr The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
title_full_unstemmed The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
title_short The Distinct Effects of Palmitic and Oleic Acid on Pancreatic Beta Cell Function: The Elucidation of Associated Mechanisms and Effector Molecules
title_sort distinct effects of palmitic and oleic acid on pancreatic beta cell function the elucidation of associated mechanisms and effector molecules
topic palmitic acid
oleic acid
human pancreatic beta cells
endoplasmic reticulum stress
inflammation
oxidative stress
url https://www.frontiersin.org/article/10.3389/fphar.2018.01554/full
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