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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 | Stabilization of All-trans-lycopene from Tomato by Encapsulation Using Cyclodextrins显示文摘 | BLANCH G P RUTZ DEL CASTILLO M L CAJA M M et at | 2007 | Food Chem2007，105，4： | 1 |
| 3 | Study of the enantiomeric composition of chiral constituents in edible oils by simultaneous distillation-extraction, detection of adulterated olive oils 显示文摘 | CAJA M M RUIZ del CASTILLO M L R HERRAIZ M | 1999 | Journal of the American Oil Chemists'' Society1999，76，9： | 1 |
| 4 | Potential of particle and fibre reinforcement of tyre tread elastomers显示文摘 | RJOS S CHICUREL R DEL CASTILLO L F | 2001 | Materials and Dcsign2001，22，： | 1 |
| 5 | 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 |
| 6 | Prospecting metal-resistant plant-growth promoting rhi- zobacteria for rhizoremediation of metal contaminated estuaries using Spatina densflora 显示文摘 | ANDRADES-MORENO L DEL CASTILLO I PARRA R | 2014 | Environ Sci Pollut Res2014，，21： | 1 |
| 7 | 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 |
| 8 | 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 |
| 9 | 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 |
| 10 | Karyotypie diversity among Blastocystis hominis isolates 显示文摘 | Carbajal JA del Castillo L Lanuza MD et ol | 1997 | Int J Para-sitol1997，27，8： | 1 |
| 11 | Human platelets contain seinderin, a Ca2+ -dependent actin filament- severing protein 显示文摘 | Rodriguez Del Castillo A Vitale ML Tchakarov L | 1992 | Thromb Haemost1992，67，2： | 1 |
| 12 | The phar- macokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics显示文摘 | Toutain P L Del Castillo J R E Bousquet-Melou A | 2002 | Res Vet Sci2002，73，2： | 1 |
| 13 | Continuous renal replacement therapy in children after cardiac surgery显示文摘 | Maria José Santiago Jesús López-Herce Javier Urbano Maria José Solana Jimena del Castillo Amelia Sánchez Jose María Bellón | 2013 | The Journal of Thoracic and Cardiovascular Surgery2013，，2： | 1 |
| 14 | Scripta Materialia显示文摘 | Wu Y Castillo Del L Lavernia E J | 1996 | 34(8)1996，1243，： | 1 |
| 15 | Clinical course and mortality risk factors incritically ill children requiring continuous renal replacement thera-py显示文摘 | Santiago MJ López-Herce J Urbano J Solana MJ del Castillo J Ballestero Y | 2010 | Intensive Care Med2010，36，5： | 1 |
| 16 | Countervailing influence of tumor necrosis factor-alpha and nitric oxide in endotoxemia 显示文摘 | del Castillo D Rutherford MS Raij L | 2001 | J Am Soc Nephrol2001，12，6： | 1 |
| 17 | Stabilization of all-trans-lycopene from tomato by encapsulation using cyclodextrins 显示文摘 | Blanch G P Ruiz Del Castillo M L Del Mar Caja M | 2007 | Food Chemistry2007，105，4： | 1 |
| 18 | Stabilization of all-trans lycopene from tomato by encapsulation using cyclodextrins显示文摘 | Blanch G P Ruiz del Castillo M L del Mar Caja M | 2007 | Food chemistry2007，105，4： | 1 |
| 19 | Catalysis Letter显示文摘 | del Castillo H L Gil A Grange P | 1997 | (43): 133-1371997，，43： | 1 |
| 20 | Neural reorganization accompanying upper limb motor rehabilitation from stroke with virtual reality-based gesture therapy显示文摘 | Orihuela-Espina F Fernández del Castillo I Palafox L | 2013 | Top Stroke Rehabil2013，20，3： | 1 |
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