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| 1 | Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology显示文摘AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical limitations.RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may helpto explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients.CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose. | Nahum Calvo Raúl Beltrán-Debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven | 2015 | World Journal of Gastroenterology2015，21，24： | 2 |
| 2 | Run-to-Run Process Control: Literature Review and Extensions显示文摘 | Del Castillo E Hurwitz A | 1997 | J of Quality Technology1997，29，2： | 1 |
| 3 | Cost- t of ventilator- associated pneumonia with linezolid or vancomycin in Spain显示文摘 | Grau S Alvarez-Lerma F del Castillo effectiveness analysis of the treatmen A | 2005 | J Chemother2005，17，2： | 1 |
| 4 | Autoerine production of TGF-beta confers resistance to apoptosis after an epithelial-mesenchymal transition process in hepatocytes: Role of EGF receptor ligands显示文摘 | Del Castillo G Murillo MM Alvarez-Barrientos A | 2006 | Exp Cell Res2006，312，15： | 1 |
| 5 | Parasitic helminths of the wild rabbit,Oryctolagus cuniculus,in different bioclimatic zones in Tenerife,Canary Islands显示文摘 | Foronda P Del Castillo A Abreu N | 2003 | J Helminthol2003，77，4： | 1 |
| 6 | Development and use of a multiplex real-time quantitative polymerase chain reaction assay for detection and differentiation of porcine circovirus-2 genotypes 2a and 2b in an epidemiological survey显示文摘 | Gagnon C A Del Castillo J R Music N | 2008 | J Vet Diagn Invest2008，20，5： | 1 |
| 7 | Antioxidantproperties of soy protein - fructooligosaccharide glycation systems and its hydrelyzates 显示文摘 | Mesa MD Silv6n J Olza J Gil A del Castillo M | 2008 | Food Research International2008，41，： | 1 |
| 8 | Luminescent properties of transparent nanostructured Eu3 + doped SnO2-SiO2 glass-ceramics prepared by the sol-gel method显示文摘 | Del Castillo J Rodríguez V D Yanes A C | 2005 | Nanotechnology2005，16，5： | 1 |
| 9 | Di agnoisis of ascending aortic dissection by transesophageal echo cardiography:utility of M mode in recognizing artifacts显示文摘 | Evangelista A Carcia del Castillo H Gonzalez Alujas T | 1996 | J Am Coll Cardiol1996，27，1： | 1 |
| 10 | Stabilization of all-trans-lycopene from tomato by encapsulationusing cyclodextrins显示文摘 | Gracia Patricia Blanch a Mar?' a Luisa Ruiz del Castillo a Mar?' a del Mar Ca | 2007 | Food Chemistry2007，，105： | 1 |
| 11 | Mononucleosis caused by Epstein-barr virus and cytomegalovirus in children: a comparative study of 124 cases显示文摘 | Lao A Borgue C Del Castillo F | 1994 | Pediatr Infect Dis J1994，13，1： | 1 |
| 12 | Chromaffin cell scinderin: A novel calcium- dependent actin filament severing protein 显示文摘 | Rodriguez Del Castillo A Lemaire S Tehakarov L | 1990 | EMBO J1990，9，1： | 1 |
| 13 | I- solation and characterization of a putative liver progenitor popula- tion after treatment of fetal pat hepatocytes with TGF-beta显示文摘 | Del Castillo G Alvarez-Barrientos A Carmona-Cuenca I | 2008 | J Cell Physiol2008，215，3： | 1 |
| 14 | Preparation and characterization of sulfated titanium-modified pillared montmorillonite显示文摘 | Del Castillo H L Gil A Grange P | 1997 | Catalysis Letters1997，43，： | 1 |
| 15 | Endothelial damage with cataract surgery techniques显示文摘 | Diac Valle D Benitez del Castillo Sanchez JM Castillo A | 1998 | J Cataract Refract Surg1998，24，5： | 1 |
| 16 | Molecular cloning and functional expression of ehromaffin cell scinderin indicates that it belongs to the family of Ca2+- dependent F-actin severing proteins 显示文摘 | Marcu M G Rodriguez del Castillo A Vitale M L | 1994 | Mol Cell Biochem1994，141，2： | 1 |
| 17 | Preparation and characteriza- tion of sulfated titanium -modified pillared montmorillonite 显示文摘 | Del Castillo H L Gil A Grange P | 1997 | Catalysis Letter1997，43，12： | 1 |
| 18 | Neodiosmin, a flavone glycoside of Citrus aurantium 显示文摘 | Del Rio J A Benavente O Castillo J | 1992 | Phytochemistry1992，31，2： | 1 |
| 19 | Naringin and neo- hesperidin levels during development of leaves, flower buds,and fruits of citrus aurantium显示文摘 | Castillo J Benavente O Del rio J A | 1992 | Plant Physiol1992，99，： | 1 |
| 20 | Lens fluorophotometry after trabeculectomy in primary open - angle glaucoma显示文摘 | Lazaro C Benitez - del - Castillo JM Castillo A | 2002 | Ophthalmology2002，109，1： | 1 |
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