title: Oleuropein attenuates hepatic steatosis induced by high-fat diet in mice.
abstract: OBJECTIVE
  Oleuropein, a secoiridoid derived from olives and olive oil, has been known to possess antimicrobial, antioxidative, and anticancer activities. The purpose of the present study was to determine whether oleuropein has a protective effect against hepatic steatosis induced by a high fat diet (HFD) and to elucidate its underlying molecular mechanisms in mice.
  
  
  METHODS
  Male C57BL/6N mice were fed a normal diet (ND), HFD, or an oleuropein-supplemented diet (OSD) for 10 weeks. The plasma and hepatic lipid levels were determined, and the hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively.
  
  
  RESULTS
  The supplementation of HFD with oleuropein reversed the HFD-induced increases in liver weight along with plasma and hepatic lipid levels in mice. The expression of Wnt10b inhibitor genes, such as secreted firizzed-related sequence protein 5 and dickkopf homolog 2, was downregulated, whereas the β-catenin protein expression was upregulated in the liver of OSD-fed mice compared to HFD-fed mice. Fibroblast growth factor receptor 1 (FGFR1), phosphoextracellular-signal-regulated kinase 1/2, cyclin D, and E2F transcription factor 1, along with several key transcription factors and their target genes involved in adipogenesis, were downregulated by oleuropein. OSD-fed mice exhibited decreased expression of the toll-like-receptor-(TLR)-mediated signaling molecules (TLR2, TLR4, and myeloid differentiation primary-response gene 88) and proinflammatory cytokines, in their livers, as compared to HFD mice.
  
  
  CONCLUSIONS
  These results suggest that the protective effects of oleuropein against HFD-induced hepatic steatosis in mice appear to be associated with the Wnt10b- and FGFR1-mediated signaling cascades involved in hepatic lipogenesis, along with the TLR2- and TLR4-mediated signaling implicated in hepatic steatosis.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Park
authors.forename: Youngshim
authors.initials: Y
authors.lastname: Choi
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D057888:Iridoid Glucosides; D039823:Iridoids; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009929:Organ Size / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; D057888:Iridoid Glucosides; D039823:Iridoids; D011714:Pyrans; D051193:Toll-Like Receptors; D051176:beta Catenin; C002769:oleuropein; D048049:Extracellular Signal-Regulated MAP Kinases