|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | 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 |
| 2 | Antiherpetic activity of a sulfated polysaccharide from Agaricus brasiliensis mycelia显示文摘 | Francielle Tramontini Gomes de Sousa Cardozo Carla Maísa Camelini Alessandra Mascarello Márcio José Rossi Ricardo José Nunes Célia Regina Monte Barardi Margarida Matos de Mendon?a Cláudia Maria Oliveira Sim?es | 2011 | Antiviral Research2011，，1： | 2 |
| 3 | Validation of an immunoperoxidase monolayer assay for total anti-Vac- cinia virus antibody titration 显示文摘 | Gerber P F Matos A C Guedes M I | 2012 | J Vet Diagn Invest2012，24，2： | 1 |
| 4 | Bioplastic production usingwood mill effluents as feedstock 显示文摘 | Ben M Mato T Lopez A | 2011 | Water Science andTechnology2011，63，6： | 1 |
| 5 | Enthalpies of combustion, vapour pressures, and enthalpies of sublimation of 8- hydroxyquinoline, 5-nitro-8-hydroxyquinoline, and 2-methyl-8-hydroxyquinoline显示文摘 | Ribeiro Da Silva M A V Monte M J S Matos M A R | 1989 | Chem Thermodyn1989，，21： | 1 |
| 6 | Removal of inorganic charged micro-pollutants in an ion-exchange membrane bioreactor 显示文摘 | Velizarov S Matos C Reis M A M | 2005 | Desalination2005，178，13： | 1 |
| 7 | Competitive adsorption of zinc,cadmium,copper and lead in three highly weathered Brazilian soils显示文摘 | Fontes M P F Matos A F Costa L M | 2000 | Commun Soil Sci Plant Anal2000，31，： | 1 |
| 8 | Survey of Mycobacterium avium subspecies paratuberculosis in road-killed wild carnivores in Portugal显示文摘 | Matos A C Figueira L Martins M H | 2014 | J Zoo Wildl Med2014，45，4： | 1 |
| 9 | Influence of limestone addition on the behavior of NO and N20 dur- ing fluidised bed coal combustion 显示文摘 | Tarelho L A C Matos M A A Pereira F J M A | 2006 | Fuel2006，85，7： | 1 |
| 10 | Diagenesis and reservoir quality evolution of fluvial sandstones during progressive burial and uplift : evi- dence from the Upper Jurassic Boipeba Member, Recrncavo basin, Northeastern Brazil显示文摘 | Salem A M Morad S Mato L F | 2000 | AAPG Bulletin2000，84，7： | 1 |
| 11 | Ultrasound -assisted treatment of pahn oil samples for the determination of copper and lead by stripping chronopotenfiometry显示文摘 | Cypriano J C Matos M A C Mates R C | 2008 | Microchem J2008，90，： | 1 |
| 12 | Loss allocation in distribution net- works with embedded generation显示文摘 | Costa P M Matos M A | 2004 | IEEE Trans on Power Systems2004，19，1： | 1 |
| 13 | Effect of relaxation and primary nanocrystallization on the mechanical properties of Cu60Zr22Ti18 bulk metallic glass显示文摘 | Concustell A Alcala G Mato S Woodcock T G Gebert A Eckert J Baro M D | 2005 | Intermetallics2005，13，： | 1 |
| 14 | Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation显示文摘 | Braga A Maest 6 I Matos M | 2015 | Gynecol Oncol2015，139，2： | 1 |
| 15 | The Colors of Investors' Money:The Role of Institutional Investors Around the World显示文摘 | Ferreira M A Matos P | 2008 | Journal of Financial Economics2008，88，： | 1 |
| 16 | Dramatic change in Citrus tristeza virus populations in the Dominican Republic显示文摘 | MATOS L A HILF M E CAYETANO X A FELIZ A O HARPER S J FOLIMONOVA S Y | 2013 | Plant Disease2013，97，： | 1 |
| 17 | A novel patatin-like gene stimulated by drought stress encodes a ga- lactolipid acyl hydrolase显示文摘 | Matos A R d' Arcy-Lameta A Franca M | 2001 | Febs Letters2001，491，3： | 1 |
| 18 | Distribution systems reconfiguration based on OPF using benders decom- position 显示文摘 | Khodr H M Martinez C J Matos M A | 2009 | IEEE Trans on Power Delivery2009，80，2： | 1 |
| 19 | The colors of investors'money: The role of institutional investors around the world 显示文摘 | FERREIRA M A MATOS P | 2008 | Journal of Financial Economics2008，88，3： | 1 |
| 20 | A ZigBeeMulti-powered Wireless Acquisition Device for Remote SensingApplications in Precision Viticulture显示文摘 | MORAIS R FEMANDES M A MATOS S G | 2008 | Computers and Electron-ics in Agriculture2008，62，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员