A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice
| Autor: | Kelli A. Lytle, Melinda H. Spooner, Donald B. Jump, Manuel García-Jaramillo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
nonalcoholic fatty liver disease
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism Membrane lipids lcsh:QR1-502 digestive system Biochemistry Article lcsh:Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Nonalcoholic fatty liver disease Lipidomics arachidonic acid medicine nonalcoholic steatohepatitis Molecular Biology mass spectrometry chemistry.chemical_classification fibrosis nutritional and metabolic diseases food and beverages docosahexaenoic acid Oxylipin medicine.disease digestive system diseases 3. Good health 030104 developmental biology Endocrinology chemistry inflammation Docosahexaenoic acid lipidomics lipids (amino acids peptides and proteins) 030211 gastroenterology & hepatology Arachidonic acid Steatosis Polyunsaturated fatty acid |
| Zdroj: | Metabolites, Vol 9, Iss 11, p 252 (2019) Metabolites Volume 9 Issue 11 |
| ISSN: | 2218-1989 |
| Popis: | Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the western diet (WD) is a major contributor to the onset and progression of these chronic diseases. Our aim was to use a lipidomic approach to identify potential lipid mediators of diet-induced NASH. We previously used a preclinical mouse (low density lipoprotein receptor null mouse, Ldlr -/-) model to assess transcriptomic mechanisms linked to WD-induced NASH and docosahexaenoic acid (DHA, 22:6, &omega 3)-mediated remission of NASH. This report used livers from the previous study to carry out ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography coupled with dynamic multi-reaction monitoring (HPLC-dMRM) to assess the impact of the WD and DHA on hepatic membrane lipid and oxylipin composition, respectively. Feeding mice the WD increased hepatic saturated and monounsaturated fatty acids and arachidonic acid (ARA, 20:4, &omega 6) in membrane lipids and suppressed &omega 3 polyunsaturated fatty acids (PUFA) in membrane lipids and &omega 3 PUFA-derived anti-inflammatory oxylipins. Supplementing the WD with DHA lowered hepatic ARA in membrane lipids and ARA-derived oxylipins and significantly increased hepatic DHA and its metabolites in membrane lipids, as well as C20&ndash 22 &omega 3 PUFA-derived oxylipins. NASH markers of inflammation and fibrosis were inversely associated with hepatic C20&ndash 3 PUFA-derived Cyp2C- and Cyp2J-generated anti-inflammatory oxylipins (false discovery rate adjusted p-value q &le 0.026). Our findings suggest that dietary DHA promoted partial remission of WD-induced NASH, at least in part, by lowering hepatic pro-inflammatory oxylipins derived from ARA and increasing hepatic anti-inflammatory oxylipins derived from C20&ndash 3 PUFA. |
| Databáze: | OpenAIRE |
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