title: Ixeris dentata decreases ER stress and hepatic lipid accumulation through regulation of ApoB secretion.
abstract: Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Mi-Rin
authors.initials: MR
authors.lastname: Lee
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Geum-Hwa
authors.initials: GH
authors.lastname: Lee
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Nan-Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D001055:Apolipoproteins B / Q000378:metabolism*; D019659:Asteraceae / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; C497249:DDIT3 protein, human; D015852:Eukaryotic Initiation Factor-2; D010168:Palmitates; D010936:Plant Extracts; D014280:Triglycerides; D051742:Transcription Factor CHOP; D002784:Cholesterol; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase