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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01554

The Distinct Effects Of Palmitic And Oleic Acid On Pancreatic Beta Cell Function: The Elucidation Of Associated Mechanisms And Effector Molecules

 Miruna Nemecz1*, Alina Constantin1, Madalina Dumitrescu1,  Nicoleta Alexandru1, Alexandru Filippi1, Gabriela Tanko1 and  Adriana Georgescu1*
  • 1Institute of Cellular Biology and Pathology (ICBP), Romania

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.

Keywords: Palmitic Acid, Oleic Acid, human pancreatic beta cells, Endoplasmic Reticulum Stress, Inflammation, Oxidative Stress

Received: 27 Jul 2018; Accepted: 20 Dec 2018.

Edited by:

Banasri Hazra, Jadavpur University, India

Reviewed by:

DR.DOMINIC O. OCHWANG'I, University of Nairobi, Kenya
Angela M. Valverde, Spanish National Research Council (CSIC), Spain  

Copyright: © 2018 Nemecz, Constantin, Dumitrescu, Alexandru, Filippi, Tanko and Georgescu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Miruna Nemecz, Institute of Cellular Biology and Pathology (ICBP), Bucharest, Romania, miruna.nemecz@icbp.ro
PhD. Adriana Georgescu, Institute of Cellular Biology and Pathology (ICBP), Bucharest, Romania, adriana.georgescu@icbp.ro