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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 | Surgical versus non - sur- gical treatment for carpal tunnel syndrome 显示文摘 | Verdugo RJ Salinas RA Castillo JL | 2008 | Coehrane Database Syst Rev2008，，00： | 1 |
| 3 | Histiocytic sarcoma: a case report and review of the literature 显示文摘 | Khosravi SP del Castillo RA | 2005 | An Med Interna2005，22，4： | 1 |
| 4 | A retrospective analysis of osseo- tire NT implants in clinical practice: 1-year foUow-up显示文摘 | Drago CJ DeI Castillo RA | 2006 | Int J Periodontics Restorative Dent2006，26，： | 1 |
| 5 | Surgical versus non-surgical treatment for carpal tunnel syndrome显示文摘 | Verdugo RJ Salinas RA Castillo JL | 2008 | Cochrane Database Syst Rev2008，4，： | 1 |
| 6 | Surgical versus non-surgical treatment for carpal tunnel syndrome显示文摘 | Verdugo RJ Salinas RA Castillo JI | 2008 | Cochrane Database Syst Rev2008，4，00： | 1 |
| 7 | The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage is susceptible to increased weight gain when fed a high-fat diet: Confirmation of a gene-diet interaction 显示文摘 | Jelinek D Castillo JJ Heidenreich RA | 2015 | Gene2015，568，1： | 1 |
| 8 | Clinical significance of fetal tachypnea during anterpartum biophysical scanning显示文摘 | Castillo RA Searle N | 1987 | Obstet Gynecol1987，69，： | 1 |
| 9 | Synthesis and antiparasitic activity of 2-(Trifluoromethyl)benzimidazole derivatives显示文摘 | Gabriel Navarrete-Vázquez Roberto Cedillo Alicia Hernández-Campos Lilián Yépez Francisco Hernández-Luis Juan Valdez Raúl Morales Rafael Cortés Manuel Hernández Rafael Castillo | 2001 | Bioorganic & Medicinal Chemistry Letters2001，，2： | 1 |
| 10 | Surgical versus nonsurgical treatment for carpal tunnel syndrome 显示文摘 | Verdugo RJ Salinas RA Castillo JL | 2008 | Cochrane Database Syst Rev2008，，00： | 1 |
| 11 | Kainate receptors mediate a slow pos tsynaptic current in hippocampal CA3 neurons 显示文摘 | Malenka RC Nicoll RA | 1997 | Nature1997，388，： | 1 |
| 12 | In vitro antifungal activity of plant extracts obtained with alternative organic solvents against Rhizoctonia solani Kühn显示文摘 | Francisco Castillo Daniel Hernández Gabriel Gallegos Martha Mendez Raúl Rodríguez Alfonso Reyes Cristóbal N. Aguilar | 2010 | Industrial Crops & Products2010，，3： | 1 |
| 13 | Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons显示文摘 | Castillo PE Malenka RC Nicoll RA | 1997 | Nature1997，388，6638： | 1 |
| 14 | Alcohol and reproductive function:a review显示文摘 | Hadi HA Hill JA Castillo RA | 1999 | Obstet Gynecol Surv1999，42，2： | 1 |
| 15 | The role of Ca^2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation 显示文摘 | Castillo PE Weisskopf MG Nicoll RA | 1994 | Neuron1994，12，： | 1 |
| 16 | Surgical versus non-surgical treatment for carpal tunnel syndrome显示文摘 | Verdugo RN Salinas RA Castillo JI | 2008 | Cochrane Database Syst Rev2008，4，00： | 1 |
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