Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models
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...
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doaj-e6351a2f24fd4878ba974a65d82e428e2020-11-24T23:33:37ZengMDPI AGMarine Drugs1660-33972017-06-0115616310.3390/md15060163md15060163Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD ModelsYouying Zhang0Tian Meng1Ling Zuo2Yu Bei3Qihao Zhang4Zhijian Su5Yadong Huang6Jiyan Pang7Qi Xiang8Hongtu Yang9Institute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaSchool of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, ChinaInstitute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pharmacy, Jinan University, Guangzhou 510632, ChinaThe 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.http://www.mdpi.com/1660-3397/15/6/163Xyloketal BNAFLDSREBP-1c pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Youying Zhang Tian Meng Ling Zuo Yu Bei Qihao Zhang Zhijian Su Yadong Huang Jiyan Pang Qi Xiang Hongtu Yang |
spellingShingle |
Youying Zhang Tian Meng Ling Zuo Yu Bei Qihao Zhang Zhijian Su Yadong Huang Jiyan Pang Qi Xiang Hongtu Yang Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models Marine Drugs Xyloketal B NAFLD SREBP-1c pathway |
author_facet |
Youying Zhang Tian Meng Ling Zuo Yu Bei Qihao Zhang Zhijian Su Yadong Huang Jiyan Pang Qi Xiang Hongtu Yang |
author_sort |
Youying Zhang |
title |
Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models |
title_short |
Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models |
title_full |
Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models |
title_fullStr |
Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models |
title_full_unstemmed |
Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models |
title_sort |
xyloketal b attenuates fatty acid-induced lipid accumulation via the srebp-1c pathway in nafld models |
publisher |
MDPI AG |
series |
Marine Drugs |
issn |
1660-3397 |
publishDate |
2017-06-01 |
description |
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. |
topic |
Xyloketal B NAFLD SREBP-1c pathway |
url |
http://www.mdpi.com/1660-3397/15/6/163 |
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