The Citrus Flavonoid Nobiletin Downregulates Angiopoietin-like Protein 3 (ANGPTL3) Expression and Exhibits Lipid-Modulating Effects in Hepatic Cells and Adult Zebrafish Models

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 生物科技系(所) > 期刊論文 > Item 310902800/34602

請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/34602

標題:	The Citrus Flavonoid Nobiletin Downregulates Angiopoietin-like Protein 3 (ANGPTL3) Expression and Exhibits Lipid-Modulating Effects in Hepatic Cells and Adult Zebrafish Models
作者:	Lin, Ching-Yen Chen, Pei-Yi Hsu, Hao-Jen Gao, Wan-Yun Wu, Ming-Jiuan Yen, Jui-Hung
貢獻者:	Tzu Chi University Buddhist Tzu Chi General Hospital Tzu Chi University Tzu Chi University Department of Biotechnology, Chia Nan University of Pharmacy & Science
關鍵字:	high-density-lipoprotein cardiovascular-disease selective uptake metabolism cholesterol lipase gene triglycerides suppresses kinase
日期:	2022
上傳時間:	2023-12-11 14:00:06 (UTC+8)
出版者:	MDPI
摘要:	Nobiletin, a dietary citrus flavonoid, exerts biological activities against hyperlipidemia, obesity, and atherosclerotic cardiovascular diseases (ASCVDs). The aim of this study was to explore the lipid-lowering effects of nobiletin and the underlying molecular mechanisms in vitro in hepatic cells and in vivo in zebrafish models. Transcriptome and gene ontology (GO) analyses of differentially expressed genes (DEGs) by gene set enrichment analysis (GSEA) showed that a set of twenty-eight core enrichment DEGs associated with GO BP regulation of lipid metabolic process (GO: 0019216) were significantly downregulated in nobiletin-treated cells. Among these genes, angiopoietin-like 3 (ANGPTL3), an inhibitor of lipoprotein lipase (LPL) activity that regulates TG-rich lipoprotein (TGRL) metabolism in circulation, was the protein most markedly downregulated by nobiletin. Nobiletin (20 and 40 mu M) significantly reduced the levels of ANGPTL3 mRNA and intracellular and secreted ANGPTL3 proteins in hepatic cell lines. Furthermore, alleviation of secreted ANGPTL3 production by nobiletin was found to reinstate LPL catalytic activity. Nobiletin significantly inhibited ANGPTL3 promoter activity and attenuated the transcription factor liver X receptor-alpha (LXR alpha)-mediated ANGPTL3 transcription. Molecular docking analysis predicted that nobiletin could bind to the ligand-binding domain of LXR alpha, thereby counteracting LXR alpha activation. In animal studies, orally administered nobiletin significantly alleviated the levels of plasma triglycerides (TGs) and cholesterol in zebrafish fed a high-fat diet. Moreover, nobiletin significantly reduced the amounts of hepatic ANGPTL3 protein in zebrafish. Our findings suggest that nobiletin may regulate the LXR alpha-ANGPTL3-LPL axis and exhibit lipid-modulating effects in vitro and in vivo. Thus, nobiletin is a potential ANGPTL3 inhibitor for the regulation of lipid metabolism to ameliorate dyslipidemia and ASCVDs.
關聯:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.20, 12485
顯示於類別:	[生物科技系(所)] 期刊論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
ijms-23-12485.pdf		5021Kb	Adobe PDF	142	檢視/開啟
index.html		0Kb	HTML	245	檢視/開啟

在CNU IR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....