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| 1 | Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments. | José M Mato Cristina Alonso Mazen Noureddin Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，24： | 19 |
| 2 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 3 | Occurrence of Organochlorine Insecticides, PCBs and PCB Congeners in waters and Sediments of the Ebro River (Spain) 显示文摘 | Fernandez M A Alonso C Gonzalez M J | 1999 | Chemosphere1999，38，： | 2 |
| 4 | 3, 5-Bis (trifluoromethyl) phenyl sulfones in the modified julia olefination: application to the synthesis of resveratrol 显示文摘 | Alonso D A Najera C Varea M | 2004 | Tetrhaedron Lett2004，45，： | 1 |
| 5 | Is cisplatin-induced cell death always produced by apoptosis?显示文摘 | GONZALEZ V M FUERTES M A ALONSO C | 2001 | Mol Pharmaeol2001，59，4： | 1 |
| 6 | On-line preconcentration using chelating and ion-exchange minicolumns for the speciation of chromium(iii) and chrontium(vi) and their quantitative determination in natural waters by inductively coupled plasma mass spectrometry显示文摘 | GUERRERO M M L ALONSO E V PAVON J M C | 2012 | Journal of Analytical Atomic Spectrometry2012，27，4： | 1 |
| 7 | New regulatory CD19 + CD25 + B-cell subset in clinically isolated syndrome and multiple sclerosis relapse Changes after glucocorticoids 显示文摘 | de Andr6s C Tejera-Alhambra M Alonso B | 2014 | J Neuroimmunol2014，270，12： | 1 |
| 8 | Chronic psychosocial stress induces reversible mitochondrial damage and corticotropin-releasing factor receptor type - 1 upregulation in the rat intestine and IBS - like gut dysfunction 显示文摘 | Vicario M Alonso C Guilarte M | 2012 | Psychoneuroendocrinology2012，37，1： | 1 |
| 9 | Prevalence of Mental Disorders in Europe: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) Project显示文摘 | Alonso J Angermeyer M C Bernert S | 2004 | Acta Psychiatry Scand Suppl2004，，420： | 1 |
| 10 | Family-based ter- ritoriality vs flocking in wintering common cranes Grus grus 显示文摘 | Alonso J C Bautista L M Alonso J A | 2004 | Journal of Avian Biology2004，35，5： | 1 |
| 11 | Ecotoxicological assessment of doxycycline in aged pig manure using multispecies soil systems 显示文摘 | FERNANDEZ C ALONSO C BABIN M M | 2004 | Science of the Total Environment2004，，323： | 1 |
| 12 | Baseline of butyltin pollution in coastal sediments within the Basque Country (northern Spain), in 2007-2008显示文摘 | Rodriguez J G~ Solaun O Larreta J Segarra M J B Franco J Alonso J I G Sariego C Valencia V Borja A | 2010 | Marine Pollution Bulletin2010，60，1： | 1 |
| 13 | Integrated Buck- flyback converter as a high-power-factor off-line power supply 显示文摘 | ALONSO J M DALLA COSTA M A ORDIZ C | 2008 | IEEE Transactions on Industry Applications2008，55，3： | 1 |
| 14 | Reactivity of highly cycled particles of CaO in a carbonation/calcination loop显示文摘 | Grasa G S Abanades J C Alonso M | 2008 | Chemical Engineering Journal2008，137，3： | 1 |
| 15 | Influence of organic adsorbates on the under and overpotential deposition of copper on polycrystalline platinum electrodes 显示文摘 | Alonso C Pascual M J Abruna a H D | 1997 | Electrochimica Acta1997，42，11： | 1 |
| 16 | The Arabidopsis histidine phosphotransfer proteins are redundant positive regulators of cytokinin signaling显示文摘 | Hutchison C.E Li J Argueso C Gonzalez M Lee E Lewis M.W Maxwell B.B Perdue T.D SchalLer G.E Alonso J.M Ecker J.R Kieber J.J | | 0，，： | 1 |
| 17 | Ziprasidone as coadjuvant treatment in resistant obsessive-compulsive disorder treatment 显示文摘 | IQLESIAS G C SANTAMARINA M S ALONSO VILLA M J | 2006 | Actas Exp Psiquiatr2006，34，4： | 1 |
| 18 | Chloride Threshold Values to Depassivate Reinforcing Bars Embedded in a Standardized OPC Mortar显示文摘 | C Alonso C Andrade M Castellote | 2000 | Cement and Concrete Research2000，30，7： | 1 |
| 19 | N: and CO2 adsorption on activated carbon fibres prepared from No-mex chars显示文摘 | Blanco Lopez M C Martinez Alonso A Tascon J M D | 2000 | Carbon2000，38，8： | 1 |
| 20 | The effect of liquid phase on VOC removal in trickle-bed biofilters显示文摘 | Zhu X Alonso C Suidan M T | 1998 | Water Science Technology1998，38，3： | 1 |
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