title: Oleuropein reduces free fatty acid-induced lipogenesis via lowered extracellular signal-regulated kinase activation in hepatocytes.
abstract: Oleuropein, a bitter glucoside found in green olive leaves, and its metabolite hydroxytyrosol display powerful antioxidant activity both in vivo and in vitro. In this study, we hypothesized that the antioxidant activity of oleuropein could attenuate hepatic steatosis. To test this hypothesis, we established steatotic hepatocytes using HepG2 and FL83B cells treated with free fatty acids (FFAs) (oleate:palmitate, 2:1). To confirm hepatic steatosis, the intracellular lipid levels were quantitatively measured by Nile Red staining, and the sizes and distributions of lipid droplets were visualized by transmission electron microscopy. The expression of PAT family proteins as well as of adipose differentiation-related protein and tail interacting protein (TIP47) was evaluated by reverse transcriptase polymerase chain reaction and immunoblotting. To examine the cellular and molecular events associated with oleuropein, annexin V/propidium iodide staining and immunoblotting were performed. Oleuropein decreased the number and size of lipid droplets in FFA-treated cells and reduced intracellular triglyceride accumulation. However, it did not affect the expression of lipid droplets-associated PAT family proteins, including adipose differentiation-related protein and TIP47. In addition, oleuropein reduced FFA-induced extracellular signal-regulated kinase activation but had no effect on c-Jun N-terminal kinase or AKT activation. Given its protective effects against FFA-induced hepatocellular steatosis, oleuropein may be a lipid-lowering agent.
authors.affiliation: WHO Collaborating Center of Viral Hepatitis and Department of Internal Medicine College of Medicine, the Catholic University of Korea, Republic of Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Hur
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Kim
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Myeong Jun
authors.initials: MJ
authors.lastname: Song
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism* / Q000517:prevention & control; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D057888:Iridoid Glucosides; D039823:Iridoids; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D031658:Olea / Q000737:chemistry*; D000070780:Perilipin-2; D000070796:Perilipin-3; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D014280:Triglycerides / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D057888:Iridoid Glucosides; D039823:Iridoids; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; C038196:PLIN3 protein, human; D000070780:Perilipin-2; D000070796:Perilipin-3; D010936:Plant Extracts; D011714:Pyrans; D014280:Triglycerides; D033921:Vesicular Transport Proteins; C002769:oleuropein; D000217:Acyltransferases; C105599:HHAT protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases