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

Abstract

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.

Distinguish fatty acids impact survival, differentiation and cellular function of periodontal ligament fibroblasts

“…We detected significantly reduced metabolic activity levels in both, PA-and OA-treated HPdL-fibroblasts compared to BSA-treated controls. BSA was used as a cell membrane-passing carrier that binds free fatty acids such as PA and OA 17,21,22 . Since several studies reported BSA-based cellular effects on specific molecular parameters, HPdLF grown in normal DMEM culture medium were additionally added as untreated controls.…”

“…An enhanced serum level in circulating fatty acids (FA) is one major characteristic of obesity, whereby the response of cells depends on the excess and type of FA 15,16 . While increased exposure to palmitic acid (PA) has been shown as being a negative regulator in various cellular contexts [17][18][19][20] , oleic acid (OA) appears to have a more beneficial cellular impact 17,21,22 . However, both fatty acids have been found to be increased in obesity and hypertriglyceridemia [23][24][25][26][27][28] .…”

LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells

“…OA increases the rate of fatty acid oxidation through sirtuin 1 and peroxisome proliferator-activated receptor gamma co-activator 1 α [ 57 ]. OA has little effect on apoptosis; however, PA leads to apoptosis and mitochondrial dysfunction [ 17 , 53 , 54 , 58 ]. Unlike OA, PA activates NF-κB signaling and induces the secretion of pro-inflammatory cytokines, such as TNFα and IL−8 [ 14 ].…”

Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes

“…As explained above, there is excess plasma FFA during obesity. The two most commonly elevated FFA are oleate and palmitate, which are unsaturated and saturated FFA, respectively [134]. The exact mechanisms behind FFA-induced impairment in each tissue are still being elucidated, but several candidates have been proposed, including mitochondrial dysfunction and oxidative stress, ceramide synthesis, ER stress, and innate immunity.…”