Protective Effects of Oleic Acid Against Palmitic Acid-Induced Apoptosis in Pancreatic AR42J Cells and Its Mechanisms

Abstract

Palmitic acid (PAM), one of the most common saturated fatty acid (SFA) in animals and plants, has been shown to induce apoptosis in exocrine pancreatic AR42J cells. In this study, we investigated cellular mechanisms underlying protective effects of oleic acid (OLA) against the lipotoxic actions of PAM in AR42J cells. Exposure of cells to long-chain SFA induced apoptotic cell death determined by MTT cell viability assay and Hoechst staining. Co-treatment of OLA with PAM markedly protected cells against PAM-induced apoptosis. OLA significantly attenuated the PAM-induced increase in the levels of pro-apoptotic Bak protein, cleaved forms of apoptotic proteins (caspase-3, PARP). On the contrary, OLA restored the decreased levels of anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL, and Mcl-1) in PAM-treated cells. OLA also induced up-regulation of the mRNA expression of Dgat2 and Cpt1 genes which are involved in triacylglycerol (TAG) synthesis and mitochondrial β-oxidation, respectively. Intracellular TAG accumulation was increased by OLA supplementation in accordance with enhanced expression of Dgat2 gene. These results indicate that restoration of anti-apoptotic/pro-apoptotic protein balance from apoptosis toward cell survival is involved in the cytoprotective effects of OLA against PAM-induced apoptosis in pancreatic AR42J cells. In addition, OLA-induced increase in TAG accumulation and up-regulation of Dgat2 and Cpt1 gene expressions may be possibly associated in part with the ability of OLA to protect cells from deleterious actions of PAM.

Oleic acid ameliorates palmitic acid induced hepatocellular lipotoxicity by inhibition of ER stress and pyroptosis

“…The most abundant saturated fatty acid present in the diet and serum is palmitic acid (PA, 16:0) [8], that is able to trigger lipotoxicity in β cells [9], hepatocytes [10], muscular cells [11], and so on. Contrarily, unsaturated fatty acids, including monounsaturated fatty acids (MUFA), are much nontoxic, and are proven able to combat PA induced lipotoxicity [12][13][14]. Human studies indicate that MUFA-rich diet has protective effects in cardiovascular risk, NAFLD and diabetes [15][16][17].…”

Modifying effects of low-intensity extremely high-frequency electromagnetic radiation on content and composition of fatty acids in thymus of mice exposed to X-rays

“…But in this group of mice there is a significant increase in the content of oleic and summary MUFA during this period, which may indicate to changes in a balance of anti-apoptotic/pro-apoptotic activity (Ahn et al 2013). Reasons for the lack of recovery of Int J Radiat Biol Downloaded from informahealthcare.com by Korea University on 12/27/14 J U S T A C C E P T E D 14 the thymus weight even in 40 days after the combined irradiation in this group of mice are unclear and require further studies at a later date after irradiation.…”

Effect of NAD on PARP-mediated insulin sensitivity in oleic acid treated hepatocytes

“…In this study, we identified a novel pathway of insulin resistance induced by lipotoxicity attributed to PARP1 activation and NAD depletion. Previous studies have suggested that OA, a monounsaturated fatty acid, exhibited a protective effect against palmitic acid‐induced apoptosis, but triggered greater steatosis than palmitic acid (Ricchi et al, ; Ahn et al, ). Herein, we found that high OA levels resulted in more lipid accumulation in HepG2 hepatocytes but didn't affect cell viability.…”