Effects of different fatty acids on BRL3A rat liver cell damage

• Published in: Journal of cellular physiology Vol. 235; no. 9; pp. 6246 - 6256
• Main Authors: Yang, Wei, Liu, Runqi, Xia, Cheng, Chen, Yuanyuan, Dong, Zhihao, Huang, Baoyin, Li, Ruirui, Li, Ming, Xu, Chuang
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2020
• Subjects: Acetyl-CoA Carboxylase - genetics; alpha-Linolenic Acid - pharmacology; Animals; Bile acids; Cells, Cultured; Chaperones; Cholesterol; Coenzyme A; Cytochromes; Damage assessment; Deposition; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Fatty Acid Synthases - genetics; Fatty acids; Fatty Acids - metabolism; Fatty Acids - pharmacology; Fatty Liver - drug therapy; Fatty Liver - metabolism; Fatty Liver - pathology; Fatty-acid synthase; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Homeostasis; Humans; Hydrogen peroxide; Linoleic Acid - pharmacology; lipid deposition; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Lipids - biosynthesis; Lipids - genetics; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; Lipoproteins, VLDL - genetics; Liver; Liver - drug effects; Liver - metabolism; Malondialdehyde; nonalcoholic fatty liver disease; Oleic Acid - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Palmitic Acid - pharmacology; Proteins; Rats; Regulators; reticulum stress; Stearic Acids - pharmacology; Synthesis; reticulum stress; nonalcoholic fatty liver disease; fatty acids; oxidative stress; lipid deposition
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29553

To evaluate the effects of fatty acids on endoplasmic reticulum (ER) stress, oxidative stress, and lipid damage. We treated BRL3A rat liver cells with, linoleic (LA), linolenic, oleic (OA), palmitic (PA), palmitoleic (POA), or stearic (SA) acid for 12 hr. The characteristics of cell lipid deposition, oxidative stress indexes, ER stress markers, nuclear factor κB p65 (NF‐κB p65), lipid synthesis and transport regulators, and cholesterol metabolism regulators were analyzed. Endoplasmic chaperones like glucose‐regulated protein 78, CCAAT‐enhancer‐binding protein, NF‐κB p65, hydrogen peroxide, and malonaldehyde in PA‐ and SA‐treated cells were significantly higher than in other treated cells. Deposition of fatty acids especially LA and POA were significantly increased than in other treated cells. De novo lipogenesis regulators sterol regulatory element‐binding protein 1c, fatty acid synthase, and acetyl‐coenzyme A carboxylase 1 (ACC1) expression were significantly increased in all fatty acid stimulation groups, and PA‐ and SA‐treated cells showed lower p‐ACC1 expression and higher scd1 expression than other fatty acid groups. Very low‐density lipoprotein synthesis and apolipoprotein B100 expression in free fatty acids treated cells were significantly lower than control. PA, SA, OA, and POA had shown significantly increased cholesterol synthesis than other treated cells. PA and SA showed the lower synthesis of cytochrome P7A1 and total bile acids than other fatty acids treated cells. Excess of saturated fatty acids led to severe ER and oxidative stress. Excess unsaturated fatty acids led to increased lipid deposition in cultured hepatocytes. A balanced fatty acid intake is needed to maintain lipid homeostasis. Saturated fatty acids (SFAs) caused more severe hepatocyte inflammation and greater endoplasmic reticulum stress and oxidative stress than unsaturated fatty acids (USFAs), however, USFAs produced more intracellular lipid droplets than SFA treatment. SFAs and monounsaturated fatty acids had shown significantly increased cholesterol synthesis compared with polyunsaturated fatty acids. A balanced fatty acid intake is needed to maintain lipid homeostasis.