Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis
| Autor: | Julian Platon, Shelly C. Lu, Juan M. Falcón-Pérez, Concetta P. Ilisso, Rebeca Mayo, Juan Anguita, Ibon Martínez-Arranz, Manuel Romero-Gómez, María L. Martínez-Chantar, Javier Crespo, Holger Sann, Jennifer E. Van Eyk, Laura delaCruz-Villar, José M. Mato, Aaron E. Robinson, Antonio Martín-Duce, Virginia Guitiérez de Juan, José Luis Lavín Trueba, Cristina Alonso, Itziar Mincholé, Mazen Noureddin, Marta Varela-Rey, Sebastiaan M. Van Liempd, Marta Iruarrizaga-Lejarreta, Nicolás Navasa, David Fernández-Ramos, Ana M. Aransay, Patricia Aspichueta |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nonalcoholic steatohepatitis Male Very low-density lipoprotein S-Adenosylmethionine Inbred C57BL Hepatitis Mice Non-alcoholic Fatty Liver Disease Nonalcoholic fatty liver disease 2.1 Biological and endogenous factors Aetiology Mice Knockout Liver Disease Fatty Acids Gastroenterology Middle Aged 1-Carbon Metabolism Metabolome Female Adult medicine.medical_specialty Knockout Chronic Liver Disease and Cirrhosis Clinical Sciences Biology Prognostic Ceramides digestive system Article Paediatrics and Reproductive Medicine Diglycerides 03 medical and health sciences Metabolomics Internal medicine medicine Animals Humans Triglycerides Mouse Model Hepatology Gastroenterology & Hepatology Neurosciences nutritional and metabolic diseases Lipid metabolism Methionine Adenosyltransferase medicine.disease Lipid Metabolism digestive system diseases Mice Inbred C57BL 030104 developmental biology Endocrinology Steatosis Steatohepatitis Digestive Diseases Biomarkers |
| Zdroj: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Gastroenterology, vol 152, iss 6 |
| ISSN: | 1528-0012 |
| Popis: | BACKGROUND & AIMS: Nonalcoholic fatty liver disease(NAFLD) is a consequence of defects in diverse metabolic pathwaysthat involve hepatic accumulation of triglycerides. Featuresof these aberrations might determine whether NAFLD progressesto nonalcoholic steatohepatitis (NASH). We investigated whetherthe diverse defects observed in patients with NAFLD are causedby different NAFLD subtypes with specific serum metabolomicprofiles, and whether these can distinguish patients with NASHfrom patients with simple steatosis. METHODS: We collectedliver and serum from methionine adenosyltransferase 1aknockout (MAT1A-KO) mice, which have chronically low levelsof hepatic S-adenosylmethionine (SAMe) and spontaneouslydevelop steatohepatitis, as well as C57Bl/6 mice (controls); themetabolomes of all samples were determined. We also analyzedserum metabolomes of 535 patients with biopsy-proven NAFLD(353 with simple steatosis and 182 with NASH) and comparedthem with serum metabolomes of mice. MAT1A-KO mice werealso given SAMe (30 mg/kg/day for 8 weeks); liver sampleswere collected and analyzed histologically for steatohepatitis. RESULTS: Livers of MAT1A-KO mice were characterized by highlevels of triglycerides, diglycerides, fatty acids, ceramides, andoxidized fatty acids, as well as low levels of SAMe and downstreammetabolites. There was a correlation between liver andserum metabolomes. We identified a serum metabolomicsignature associated with MAT1A-KO mice that also was presentin 49% of the patients; based on this signature, we identified 2NAFLD subtypes. We identified specific panels of markers thatcould distinguish patients with NASH from patients with simplesteatosis for each subtype of NAFLD. Administration of SAMereduced features of steatohepatitis in MAT1A-KO mice. CONCLUSIONS:In an analysis of serum metabolomes of patientswith NAFLD and MAT1A-KO mice with steatohepatitis, weidentified 2 major subtypes of NAFLD and markers that differentiatesteatosis from NASH in each subtype. These might beused to monitor disease progression and identify therapeutictargets for patients. |
| Databáze: | OpenAIRE |
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