Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes

Yong Zhang,Xia Yang,Lei Dong,Jian Bai,Hongyang Shi

doi:10.1186/1476-511x-10-122

Yong Zhang, Xia Yang + Show 3 more

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https://doi.org/10.1186/1476-511x-10-122

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Abstract

BackgroundHepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of saturated and unsaturated fatty acids (FA) on apoptosis in primary rat hepatocytes.MethodsThe primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels were detected after the treatment.ResultsThe treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR)-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid.Conclusionsα-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease [1,2] that illustrates a variety of symptoms, ranging from mild steatosis, nonalcoholic steatohepatitis to cirrhosis in the liver
We report that: (1) The characteristics of palmitic acid-mediated endoplasmic reticulum (ER) stress and apoptosis in primary hepatocytes; (2) a-linolenic acid could provide protection against the cell death induced by palmitic acid; (3) Take the role of glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) expression and induction of CCAAT/enhancer-binding protein homologous protein (CHOP) into consideration, the beneficial effects were mediated via modification of the ER stress process with specific attention
The mode of cell death observed at this concentration of palmitic acid was a combination of apoptosis and necrosis, which is observed using a combination of Hoechst 33342-propidium iodide (HPI) staining (Figure 1B)

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease [1,2] that illustrates a variety of symptoms, ranging from mild steatosis, nonalcoholic steatohepatitis to cirrhosis in the liver. It affects millions of people all over the world, the etiology of NAFLD is still unknown. Certain saturated fatty acids (FA) such as palmitic acid can induce endoplasmic reticulum (ER) stress and apoptosis in rat and human liver cell lines [4,5,6,7,8], leading to inflammation and/or degeneration in the liver. We investigated the effects of saturated and unsaturated fatty acids (FA) on apoptosis in primary rat hepatocytes

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