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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 | Calpain activity in the rat brain after transient forebrain ischemia 显示文摘 | NEUMAR R W MENG F H MILLS A M | 2001 | Exp Neurol2001，170，1： | 1 |
| 3 | The keystone species concept in ecology and conservation显示文摘 | MILLS L S SOULE M E DOAK D F | 1993 | Biol Science1993，43，2： | 1 |
| 4 | SNS-595, a naphthyridine cell cycle inhibitor and stimulator of apoptosis for the treatment of cancers显示文摘 | Mills D A Fekrazad H M Verschraegen C F | 2008 | Current Opinion in Investigational Drugs2008，9，6： | 1 |
| 5 | Effect of polymerization on particle morphology in heterogeneous systems显示文摘 | MILLS M F GIBERT R G NAPPER D H | 1990 | Macromolecules1990，，23： | 1 |
| 6 | The fine structure obliquely striated body wall muscles in the earthworm,Lumbricus terrestris显示文摘 | Knapp M F | 1970 | Journal of Cell Science1970，，7： | 1 |
| 7 | The fine structure obliquely striated body wall muscles in the earthworm,Lumbricus terrestri 显示文摘 | Knapp M F | 1970 | Journal of Cell Science1970，，7： | 1 |
| 8 | The keystone-species concept in ecology and conservation显示文摘 | Mills L S Soule M E Doak D F | 1993 | BioScience1993，43，4： | 1 |
| 9 | Initiator efficiency in ATRP:The tosyl chloride/CuBr/PMDETA system显示文摘 | GURR P A MILLS M F QIAO G G | 2005 | Polymer2005，46，： | 1 |
| 10 | Effects of high hydrostatic pressure on Clostridium sporogenes spores显示文摘 | MILLS G EAMSHAW R PATTERSON M F | 1998 | Letter in Applied Microbiology1998，26，3： | 1 |
| 11 | Insights into recently fragmented vole populations from combined genetic and domographic data显示文摘 | Tallmon D A Draheim H M Mills L S Allendorf F W | 2002 | Molecular Ecology2002，11，： | 1 |
| 12 | Evolutionary relationships of the New Caledonian heterotrophic conifer, Parasitaxus usta (Podocarpaceae), inferred from chloroplast trnL-F intron/spacer and nuclear rDNA ITS2sequences显示文摘 | SINCLAIR W T MILL R R GARDNER M F | 2002 | Plant Syst Evol2002，233，： | 1 |
| 13 | Chloramphenicol-induced phenytoin intoxication显示文摘 | Vincent F M Mills L Sullivan J K | 1978 | Ann Neurol1978，3，5： | 1 |
| 14 | Muhiphase catalytic reactors : A perspective on current knowledge and future trends显示文摘 | Dudukovi6 M P Larachi F Mills P L | 2002 | Catalysis Reviews2002，44，1： | 1 |
| 15 | 查看详情显示文摘 | Babonneau D Primout M Girard F Jadaud J P Naudy M Villette B Depierreux S Blancard C Faussurier G Fournier K B Suter L Kauffman R Glenzer S Mille M C Grün J Davis J | | 0，，： | 1 |
| 16 | Nicotinamide mononu- cleotide, a key NAD (+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice显示文摘 | Yoshino J Mills K F Yoon M J | 2011 | Cell Metab2011，14，4： | 1 |
| 17 | Continent urinary diversion显示文摘 | Burkhard F C Kessler T M Mills R | 2006 | Crit Rev Oncol Hematol2006，57，： | 1 |
| 18 | Knowledge comparison in design repositories 显示文摘 | Ma Z M Mill F | 2003 | Engineering Applications of Artificial Intelligence2003，16，3： | 1 |
| 19 | Initiator Efficiency in ATRP: the Tosyl Chloride/CuBr/PMDETA System 显示文摘 | Gurr P A Mill M F Qiao G G | 2005 | Polymer2005，46，： | 1 |
| 20 | Interfer- ence suppression characterization for spectrally modu- lated, spectrally encoded signals 显示文摘 | Roberts M L Temple M A Mills R F | 2006 | IEE electronic letters2006，42，19： | 1 |
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