Betatrophin在非酒精性脂肪性肝病发病中的研究进展
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摘要
非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是肝功能障碍最常见的原因之一,与肥胖和代谢紊乱高度相关。然而肝脂肪变性的发病机制十分复杂,尤其是肝细胞和肝细胞因子之间的相互作用尚未完全阐明。促代谢因子或者血管紧张素蛋白8(又称Betatrophin)作为新型的肝细胞因子,其通过调节三酰甘油(TG)代谢、胰岛素抵抗(insulin resistance,IR)和炎症,参与NAFLD的形成。
Non-alcoholic fatty liver disease(NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with obesity and metabolic disturbance. The complex pathogenesis of NAFLD, especially the interaction between hepatocytes and hepatokines has not been fully elucidated. Betatrophin, as a novel hepatokines, are likely to be involved in the pathogenesis of NAFLD via modulating triglyceride metabolism,insulin resistance and inflammation.
Non-alcoholic fatty liver disease(NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with obesity and metabolic disturbance. The complex pathogenesis of NAFLD, especially the interaction between hepatocytes and hepatokines has not been fully elucidated. Betatrophin, as a novel hepatokines, are likely to be involved in the pathogenesis of NAFLD via modulating triglyceride metabolism,insulin resistance and inflammation.
引文
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4.Zhang R.Lipasin,a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J].Biochem Biophys Res Commun,2012,424(4):786-792.
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7.Lu P,Chen X,Zhang Z,et al.Insulin upregulates Betatrophin expression via PI3K/Akt pathway[J].Sci Rep,2017,7(1):5594.
8.Quagliarini F,Wang Y,Kozlitina J,et al.Atypical angiopoietin-like protein that regulates ANGPTL3[J].Proc Natl Acad Sci USA,2012,109(48):19751-19756.
9.Haller JF,Mintah IJ,Shihanian LM,et al.ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance[J].J Lipid Res,2017,58(6):1166-1173.
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11.Lee YH,Lee SG,Lee CJ,et al.Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease:animal and human studies[J].Sci Rep,2016,6:24013.
12.Gusarova V,Banfi S,Alexa-Braun CA,et al.ANGPTL8 blockade with a monoclonal antibody promotes triglyceride clearance,energy expenditure,and weight loss in mice[J].Endocrinology,2017,158(5):1252-1259.
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14.Gurel H.Betatrophin in nonalcoholic fatty liver disease[J].Eur JGastroenterol Hepatol,2016,28(4):487-488.
15.Hu W,Shao X,Guo D,et al.Relationship of serum betatrophin with nonalcoholic fatty liver in a Chinese population[J].PLoS One,2017,12(1):e0170758.
16.Hong BS,Liu J,Zheng J,et al.Angiopoietin-like protein 8/Betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients[J].J Diabetes Investig,2018,9(4):952-958.
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22.Fu Z,Abou-Samra AB,Zhang R.A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase[J].Sci Rep,2015,5:18502.
23.Dang F,Wu R,Wang P,et al.Fasting and feeding signals control the oscillatory expression of angptl8 to modulate lipid metabolism[J].Sci Rep,2016,6:36926.
24.Zhang Y,Li S,Donelan W,et al.Angiopoietin-like protein 8(Betatrophin)is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase[J].Biochim Biophys Acta,2016,1861(2):130-137.
25.Lee J,Hong SW,Park SE,et al.AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells[J].Mol Cell Endocrinol,2015,414:148-155.
26.Tseng YH,Ke PY,Liao CJ,et al.Chromosome 19 open reading frame80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism[J].Autophagy,2014,10(1):20-31.
27.Luo D,Chen X,Yang W,et al.Angiopoietin-like 8 improves insulin resistance and attenuates adipose tissue inflammation in diet-induced obese mice[J].Exp Clin Endocrinol Diabetes,2018,Epub ahead of print.
28.Rong Guo X,Li Wang X,Chen Y,et al.ANGPTL8/Betatrophin alleviates insulin resistance via the Akt-GSK3beta or Akt-FoxO1pathway in HepG2 cells[J].Exp Cell Res,2016,345(2):158-167.
29.Zhang Y,Guo X,Yan W,et al.ANGPTL8 negatively regulates NF-kappaB activation by facilitating selective autophagic degradation of IKKgamma[J].Nat Commun,2017,8(1):2164.
30.Bozic M,Guzmán C,Benet M,et al.Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis[J].J Hepatol,2016,65(4):748-757.
2.Dong XY,Pang XW,Yu ST,et al.Identification of genes differentially ex pressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method[J].Int J Cancer,2004,112(2):239-248.
3.Ren G,Kim JY,Smas CM.Identification of RIFL,a novel adipocyteenriched insulin target gene with a role in lipid metabolism[J].Am JPhysiol Endocrinol Metab,2012,303:E334-E351.
4.Zhang R.Lipasin,a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J].Biochem Biophys Res Commun,2012,424(4):786-792.
5.Yi P,Park JS,Melton DA.Betatrophin:a hormone that controls pancreatic beta cell proliferation[J].Cell,2013,153(4):747-758.
6.Jiao Y,Le Lay J,Yu M,et al.Elevated mouse hepatic Betatrophin expression does not increase human beta-cell replication in the transplant setting[J].Diabetes,2014,63(4):1283-1288.
7.Lu P,Chen X,Zhang Z,et al.Insulin upregulates Betatrophin expression via PI3K/Akt pathway[J].Sci Rep,2017,7(1):5594.
8.Quagliarini F,Wang Y,Kozlitina J,et al.Atypical angiopoietin-like protein that regulates ANGPTL3[J].Proc Natl Acad Sci USA,2012,109(48):19751-19756.
9.Haller JF,Mintah IJ,Shihanian LM,et al.ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance[J].J Lipid Res,2017,58(6):1166-1173.
10.Siddiqa A,Ahmad J,Ali A,et al.Structural characterization of ANGPTL8(Betatrophin)with its interacting partner lipoprotein lipase[J].Comput Biol Chem,2016,61:210-220.
11.Lee YH,Lee SG,Lee CJ,et al.Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease:animal and human studies[J].Sci Rep,2016,6:24013.
12.Gusarova V,Banfi S,Alexa-Braun CA,et al.ANGPTL8 blockade with a monoclonal antibody promotes triglyceride clearance,energy expenditure,and weight loss in mice[J].Endocrinology,2017,158(5):1252-1259.
13.Chi X,Britt EC,Shows HW,et al.ANGPTL8 promotes the ability of ANGPTL3 to bind and inhibit lipoprotein lipase[J].Mol Metab,2017,6(10):1137-1149.
14.Gurel H.Betatrophin in nonalcoholic fatty liver disease[J].Eur JGastroenterol Hepatol,2016,28(4):487-488.
15.Hu W,Shao X,Guo D,et al.Relationship of serum betatrophin with nonalcoholic fatty liver in a Chinese population[J].PLoS One,2017,12(1):e0170758.
16.Hong BS,Liu J,Zheng J,et al.Angiopoietin-like protein 8/Betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients[J].J Diabetes Investig,2018,9(4):952-958.
17.Battal F,Türk?n H,Aylan?N,et al.Investigation of blood betatrophin levels in obese children with non-alcoholic fatty liver disease[J].Pediatr Gastroenterol Hepatol Nutr,2018,21(2):111-117.
18.Mele C,Grugni G,Mai S,et al.Circulating angiopoietin-like 8(ANGPTL8)is a marker of liver steatosis and is negatively regulated by Prader-Willi syndrome[J].Sci Rep,2017,7(1):3186.
19.Cengiz M,Ozenirler S,Kocabiyik M.Serum beta-trophin level as a new marker for noninvasive assessment of nonalcoholic fatty liver disease and liver fibrosis[J].Eur J Gastroenterol Hepatol,2016,28(1):57-63.
20.García-Monzón C,Petrov PD,Rey E,et al.Angiopoietin-like protein 8is a novel vitamin D receptor target gene involved in nonalcoholic fatty liver pathogenesis[J].Am J Pathol,2018,188(12):2800-2810.
21.Vatner DF,Goedeke L,Camporez JG,et al.Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents[J].Diabetologia,2018,61(6):1435-1446.
22.Fu Z,Abou-Samra AB,Zhang R.A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase[J].Sci Rep,2015,5:18502.
23.Dang F,Wu R,Wang P,et al.Fasting and feeding signals control the oscillatory expression of angptl8 to modulate lipid metabolism[J].Sci Rep,2016,6:36926.
24.Zhang Y,Li S,Donelan W,et al.Angiopoietin-like protein 8(Betatrophin)is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase[J].Biochim Biophys Acta,2016,1861(2):130-137.
25.Lee J,Hong SW,Park SE,et al.AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells[J].Mol Cell Endocrinol,2015,414:148-155.
26.Tseng YH,Ke PY,Liao CJ,et al.Chromosome 19 open reading frame80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism[J].Autophagy,2014,10(1):20-31.
27.Luo D,Chen X,Yang W,et al.Angiopoietin-like 8 improves insulin resistance and attenuates adipose tissue inflammation in diet-induced obese mice[J].Exp Clin Endocrinol Diabetes,2018,Epub ahead of print.
28.Rong Guo X,Li Wang X,Chen Y,et al.ANGPTL8/Betatrophin alleviates insulin resistance via the Akt-GSK3beta or Akt-FoxO1pathway in HepG2 cells[J].Exp Cell Res,2016,345(2):158-167.
29.Zhang Y,Guo X,Yan W,et al.ANGPTL8 negatively regulates NF-kappaB activation by facilitating selective autophagic degradation of IKKgamma[J].Nat Commun,2017,8(1):2164.
30.Bozic M,Guzmán C,Benet M,et al.Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis[J].J Hepatol,2016,65(4):748-757.