title: Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδRegulation in Hyperlipidemic and Hypertensive Conditions.
abstract: To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδantagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1αpathway.
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Yong-Jik
authors.identifier: 0000-0001-8814-0099
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Yoo-Na
authors.initials: YN
authors.lastname: Jang
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Yoon-Mi
authors.initials: YM
authors.lastname: Han
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, 80 Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea; The Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology, Seoul, Republic of Korea.
authors.forename: Hong Seog
authors.identifier: 0000-0003-2346-0299
authors.initials: HS
authors.lastname: Seo