Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting | |
Gu, Qilin1,2; Yang, Xiaojie1,2; Lin, Li3; Li, Shaoyang3; Li, Qing1; Zhong, Shan3; Peng, Jinrong4; Cui, Zongbin1 | |
2014-12-01 | |
Source Publication | HEPATOLOGY
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ISSN | 0270-9139 |
Volume | 60Issue:6Pages:1929-1941 |
Abstract | 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. |
Subtype | Article |
Keyword | Fatty Liver-disease Magnetic-resonance Elastography Nonalcoholic Steatohepatitis Noninvasive Evaluation Stiffness Measurement Mr Elastography Natural-history United-states Xl Probe Fibrosis |
DOI | 10.1002/hep.27356 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Gastroenterology & Hepatology |
WOS Subject | Gastroenterology & Hepatology |
WOS ID | WOS:000345517000058 |
WOS Keyword | FATTY LIVER-DISEASE ; MAGNETIC-RESONANCE ELASTOGRAPHY ; NONALCOHOLIC STEATOHEPATITIS ; NONINVASIVE EVALUATION ; STIFFNESS MEASUREMENT ; MR ELASTOGRAPHY ; NATURAL-HISTORY ; UNITED-STATES ; XL PROBE ; FIBROSIS |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/342005/20374 |
Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
Affiliation | 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 |
Recommended Citation 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. |
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