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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 | Configurations used in the design of screen- printed enzymatic biosensors显示文摘 | Albareda - Sivent M Merkoci A Alegret S | 2000 | A review Sens Actuators B2000，69，： | 1 |
| 3 | Pleiotropic effects of statins and related pharmacological experimental approaches 显示文摘 | Alegret M SilAestre JS | 2006 | Methods Find Exp Clin Pharmacol2006，28，： | 1 |
| 4 | Pesticide determination in tap water and juice samples using disposable amperometric biosensors made using thick-film technology显示文摘 | Albareda-Sirvent M Merkoci A Alegret S | 2001 | Analytica Chimica Acta2001，442，： | 1 |
| 5 | Visuospatial deficits in Parkinson's disease assessed by judgment line orientation test: error analyses and practice effects显示文摘 | Alegret M Vendrell P Junque C | 2001 | J Clin Exp Neuro- psychol2001，23，： | 1 |
| 6 | Application of a potentiometric electronic tongue as a classification tool in food analysis显示文摘 | Gallardo J Alegret S Valle M D | 2005 | Talanta2005，66，： | 1 |
| 7 | 显示文摘 | SANTANDREU M ALEGRET S FABREGAS E | 1999 | Anal Chim Acta1999，396，23： | 1 |
| 8 | Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insight显示文摘 | Laguna J C Alegret M Roglans N | 2014 | Nutrients2014，6，12： | 1 |
| 9 | Pesticide determination in tap water and juice samples using disposable amperometric biosensor made using thick film technology显示文摘 | Albareda Sirvent M Merkoci A Alegret S | 2001 | Anal Chim Acta2001，442，： | 1 |
| 10 | Carbon nanotubeepoxy composite for electrochemical sensing 显示文摘 | Pumera M Merkoci A Alegret S | 2006 | Sens Actuators B2006，113，： | 1 |
| 11 | Pesticide determination in tap water and juice samples using disposable amperometrie bioseusors made using thick-film technology显示文摘 | Albareda-Sirvent M Merkoci A Alegret S | 2001 | Anal Chim Acta2001，442，： | 1 |
| 12 | Effects of bilateral subthalamic stimu- lation on cognitive function in Parkinson disease显示文摘 | Alegret M Junque C | 2001 | Arch Neurol2001，58，： | 1 |
| 13 | Application of a potentiometric electronic tongue to fertigation strategy in greenhouse cultivation显示文摘 | Guti′errez M Alegret S aceres R C′ | 2007 | Computers and Electronics in Agriculture2007，57，1： | 1 |
| 14 | Amperometric Immunosensors Based on Rigid Conducting Immunocomposites显示文摘 | Cespedes F Alegret S Esteve Martínez-F | 1997 | Anal Chem1997，69，： | 1 |
| 15 | Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer disease from mild cognitive impairment 显示文摘 | Alegret M Cuberas-Borros G Espinosa A | 2014 | J Alzheimers Dis2014，41，3： | 1 |
| 16 | Configurations used in the design of screen-printed enzymatic biosensors 显示文摘 | Albareda S M Merkoci A Alegret S | 2000 | A re- view Sens Aetuat2000，69，： | 1 |
| 17 | Lead (II) ion selective elec- trodes with PVC membranes based on two bis - thioureas as ionophores : 1,3 - bis( N' - benzoyhhioureido) benzene and 1,3 - bis( N' - furoyl- thioureido)benzene显示文摘 | Wilson D Arada M A Alegret S | 2010 | J Hazard Mater2010，181，13： | 1 |
| 18 | Pleiotropic effects of statins and related pharmacological experimental approaches 显示文摘 | Alegret M Silvestre J S | 2006 | Methods Find Exp Clin Pharmacol2006，28，9： | 1 |
| 19 | Pesticide determination in tap water and juice samples using disposable amperometric biosensors made using thick film technology 显示文摘 | Albareda-Sirvent M Merkoci A Alegret S | 2001 | Anal Chim Acta2001，，442： | 1 |
| 20 | Increased reactive oxygen species production down-regulates peroxisome proliferator-activated alpha pathway in C2C12 skeletal muscle cells 显示文摘 | CABRERO A ALEGRET M SANCHEZ RM | 2002 | J Biol Ghem2002，277，10： | 1 |
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