Science & Technology
; Life Sciences & Biomedicine
类目[WOS]:
Gastroenterology & Hepatology
研究领域[WOS]:
Gastroenterology & Hepatology
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.
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:
Gu, Qilin; Yang, Xiaojie; Lin, Li; Li, Shaoyang; Li, Qing; Zhong, Shan; Peng, Jinrong; Cui, Zongbin.Genetic Ablation of Solute Carrier Family 7a3a Leads to Hepatic Steatosis in Zebrafish During Fasting,HEPATOLOGY,2014,():
