Oleuropein prevents the progression of steatohepatitis to hepatic fibrosis induced by a high-fat diet in mice.
Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (α-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, α-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans.
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Sung Woo
SW
Kim
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Wonhee
W
Hur
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Tian Zhu
TZ
Li
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Young Ki
YK
Lee
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Jung Eun
JE
Choi
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Sung Woo
SW
Hong
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Kwang-Soo
KS
Lyoo
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Chan Ran
CR
You
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Eun Sun
ES
Jung
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Chan Kun
CK
Jung
Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.
Taesun
T
Park
Department of Bioscience and Biotechnology/Institute of Bioscience, Sejong University, Seoul, Republic of Korea.
Soo-Jong
SJ
Um
Department of Internal Medicine and Catholic University Liver Research Center, Seoul, Republic of Korea.
Seung Kew
SK
Yoon
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D057888:Iridoid Glucosides; D039823:Iridoids / Q000627:therapeutic use*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
D000199:Actins; D000959:Antihypertensive Agents; D024042:Collagen Type I; D057888:Iridoid Glucosides; D039823:Iridoids; D020738:Leptin; C544013:alpha-smooth muscle actin, mouse; C002769:oleuropein