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Mar. Drugs 2017, 15(6), 163; doi:10.3390/md15060163

Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models

1
Institute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, China
2
Department of Pharmacy, Jinan University, Guangzhou 510632, China
3
School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China
4
The People’s Hospital of Shenzhen City, Shenzhen 518020, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Antonio Trincone, Se‐Kwon Kim and Peer B. Jacobson
Received: 8 February 2017 / Revised: 27 May 2017 / Accepted: 1 June 2017 / Published: 3 June 2017
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Abstract

The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks. Xyloketal B significantly improved HFD+HFL-induced hepatic histological lesions and attenuated lipid and glucose accumulation in the blood as well as lipid accumulation in the liver. Xyloketal B increased the expression of CPT1A, and decreased the expression of SREBP-1c and its downstream targeting enzymes such as ACC1, ACL, and FAS. Xyloketal B also significantly reduced lipid accumulation in HepG2 cells treated with free fatty acids (FFAs). These data suggested that xyloketal B has lipid-lowering effects via the SREBP-1c pathway that regulate lipid metabolism. Thus, targeting SREBP-1c activation with xyloketal B may be a promising novel approach for NAFLD treatment. View Full-Text
Keywords: Xyloketal B; NAFLD; SREBP-1c pathway Xyloketal B; NAFLD; SREBP-1c pathway
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, Y.; Meng, T.; Zuo, L.; Bei, Y.; Zhang, Q.; Su, Z.; Huang, Y.; Pang, J.; Xiang, Q.; Yang, H. Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models. Mar. Drugs 2017, 15, 163.

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