Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2014; 20(33): 11753-11761
Published online Sep 7, 2014. doi: 10.3748/wjg.v20.i33.11753
Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance
Ho Hyun Nam, Dae Won Jun, Hye Joon Jeon, Jai Sun Lee, Waqar Khalid Saeed, Eun Kyung Kim
Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea
Dae Won Jun, Hye Joon Jeon, Waqar Khalid Saeed, Department of Internal Medicine, Hanyang University School of Medicine, Seoul 133-791, South Korea
Eun Kyung Kim, Department of Pathology, Eulji University College of Medicine, Seoul 139-872, South Korea
Author contributions: Jun DW had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; Nam HH, Jun DW and Saeed WK conceived and designed the study; Nam HH, Jeon HJ and Lee JS provided animal care and molecular work; Kim EK performed histological data analysis; Saeed WK provided English editing and writing.
Supported by Research fund of the National Research Foundation of Korea 2011-0007127
Correspondence to: Dae Won Jun, MD, Department of Internal Medicine, Hanyang University School of Medicine, Hangdang dong 17,133-070, Seongdong-gu, Seoul 133-791, South Korea. noshin@hanyang.ac.kr
Telephone: +82-2-22908334 Fax: +82-2-22989183
Received: November 6, 2013
Revised: January 15, 2014
Accepted: May 19, 2014
Published online: September 7, 2014
Processing time: 305 Days and 5.6 Hours
Abstract

AIM: To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis.

METHODS: Sprague-Dawley rats (n = 30) were randomly divided into control, non-alcoholic fatty liver disease (NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk. Immunohistochemical (4-HNE, F4/80) and hematoxylin and eosin (HE) staining were performed on liver tissue extracts after animal sacrifice at 14 wk. SREBP1c, FAS, SCD-1, PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 mRNA expressions were assessed with reverse transcription-polymerase chain reaction.

RESULTS: HE staining revealed that, compared with the NAFLD group, the osthol group showed significantly decreased intrahepatic fat content (39.4% vs 21.0%; P = 0.021). SREBP1c expression in the NAFLD group increased compared to controls (P = 0.0001), while osthol treatment decreased SREBP1c expression compared with the NAFLD group (P = 0.0059). In the osthol group, intrahepatic FAS and SCD-1, which act downstream of SREBP1c, decreased significantly compared with the NAFLD group. Moreover, PPAR-α expression in the osthol group was also significantly higher than in the NAFLD group (P = 0.0147).

CONCLUSION: Osthol treatment attenuated liver steatosis by decreasing de novo liver triglyceride synthesis and had nominal effects on insulin resistance and liver inflammation.

Keywords: Osthol; Non-alcoholic fatty liver disease; Sterol regulatory element binding protein

Core tip: Nonalcoholic fatty liver disease is considered as a consequence of “multi-hit” processes. Osthol, a coumarin compound, has anti-inflammatory effects on various diseases. However, there is no multi-faceted and comprehensive evaluation of its effects. The current study evaluated effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis.