Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting

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	Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting
	Gu, Qilin 1,2; Yang, Xiaojie 1,2; Lin, Li 3; Li, Shaoyang 3; Li, Qing 1; Zhong, Shan 3; Peng, Jinrong 4; Cui, Zongbin 1
刊名	HEPATOLOGY
	2014-12-01
卷号	60 期号:6 页码:1929-1941
关键词	FATTY LIVER-DISEASE MAGNETIC-RESONANCE ELASTOGRAPHY NONALCOHOLIC STEATOHEPATITIS NONINVASIVE EVALUATION STIFFNESS MEASUREMENT MR ELASTOGRAPHY NATURAL-HISTORY UNITED-STATES XL PROBE FIBROSIS
ISSN号	0270-9139
英文摘要	Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder caused by abnormal lipid metabolisms, such as reduced hepatic fatty acid oxidation (FAO), but intracellular control of FAO under physio-and pathological conditions remains largely undefined. Here, we demonstrate that deprivation of Slc7a3a leads to hepatic steatosis in fasted zebrafish as a result of defects in arginine-dependent nitric oxide (NO) synthesis. Fast-induced hepatic steatosis in slc7a3a-null mutants can be rescued by treatments with NO donor, cyclic guanosine monophosphate analog, adenosinemonophosphate- activated protein kinase (AMPK) activator, or peroxisome proliferatoractivated receptor alpha (PPAR-alpha) agonist. In contrast, inhibitors of NO synthases, AMPK, or soluble guanylate cyclase and liver-specifically expressed dominant negatives of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and PPAR-alpha are sufficient to induce hepatic steatosis in fasted wild-type larvae. Moreover, knockdown of Slc7a3 in mice or SLC7A3 in human liver cells impaired AMPK-PPAR-alpha signaling and resulted in lipid accumulation under fasting or glucose starvation, respectively. Conclusion: These findings have revealed a NO-AMPK-PPAR-alpha-signaling pathway that is crucial for the control of hepatic FAO in vertebrates.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Gastroenterology & Hepatology
研究领域[WOS]	Gastroenterology & Hepatology
关键词[WOS]	FATTY LIVER-DISEASE ; MAGNETIC-RESONANCE ELASTOGRAPHY ; NONALCOHOLIC STEATOHEPATITIS ; NONINVASIVE EVALUATION ; STIFFNESS MEASUREMENT ; MR ELASTOGRAPHY ; NATURAL-HISTORY ; UNITED-STATES ; XL PROBE ; FIBROSIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000345517000058
公开日期	2015-01-20
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/20374]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Wuhan Univ, Wuhan 430072, Peoples R China 4.Zhejiang Univ, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Gu, Qilin,Yang, Xiaojie,Lin, Li,et al. Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting[J]. HEPATOLOGY,2014,60(6):1929-1941.
APA	Gu, Qilin.,Yang, Xiaojie.,Lin, Li.,Li, Shaoyang.,Li, Qing.,...&Cui, Zongbin.(2014).Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting.HEPATOLOGY,60(6),1929-1941.
MLA	Gu, Qilin,et al."Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting".HEPATOLOGY 60.6(2014):1929-1941.