Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways
Journal
Nutrition Research
Journal Volume
52
Pages
87-97
Date Issued
2018
Author(s)
Chen K.-Y.
Lin J.-A.
Yao H.-Y.
Hsu A.-C.
Tai Y.-T.
Chen J.-T.
Hsieh M.-C.
Hsu R.-Y.
Wu H.-T.
Wang G.H.
Ho B.-Y.
Chen Y.-P.
Abstract
Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation–associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation–associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression. ? 2018 Elsevier Inc.
Subjects
Arctigenin; Inflammation; Lipotoxicity; Nonalcoholic fatty liver disease; Steatosis
SDGs
Other Subjects
acetyl coenzyme A carboxylase; arctigenin; carnitine palmitoyltransferase I; hydroxymethylglutaryl coenzyme A reductase kinase; intercellular adhesion molecule 1; interleukin 1beta; interleukin 6; interleukin 6 receptor alpha; interleukin 7; interleukin 8; oleic acid; peroxisome proliferator activated receptor alpha; phosphatidylinositol 3 kinase; protein kinase B; sterol regulatory element binding protein 1; acetyl coenzyme A carboxylase; arctigenin; carnitine palmitoyltransferase; furan derivative; hydroxymethylglutaryl coenzyme A reductase kinase; intercellular adhesion molecule 1; interleukin derivative; lignan; oleic acid; peroxisome proliferator activated receptor alpha; phosphatidylinositol 3 kinase; plant extract; protein kinase B; sterol regulatory element binding protein 1; Article; bioaccumulation; cell survival; controlled study; enzyme activation; human; human cell; in vitro study; inflammation; lipid metabolism; lipid oxidation; lipid peroxidation; lipid storage; lipotoxicity; nonalcoholic fatty liver; priority journal; protein expression; protein phosphorylation; quantitative analysis; reverse transcription polymerase chain reaction; WRL 68 cell line; Arctium; chemistry; cytology; drug effect; fatty liver; Hep-G2 cell line; inflammation; liver; liver cell; metabolism; nonalcoholic fatty liver; oxidative stress; pathology; phytotherapy; signal transduction; Acetyl-CoA Carboxylase; AMP-Activated Protein Kinases; Arctium; Carnitine O-Palmitoyltransferase; Fatty Liver; Furans; Hep G2 Cells; Hepatocytes; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukins; Lignans; Liver; Non-alcoholic Fatty Liver Disease; Oleic Acid; Oxidative Stress; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; PPAR alpha; Proto-Oncogene Proteins c-akt; Signal Transduction; Sterol Regulatory Element Binding Protein 1
Type
journal article