Academic Journal
Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice
| العنوان: | Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice |
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| المؤلفون: | Cartland, SP, Harith, HH, Genner, SW, Dang, L, Cogger, VC, Vellozzi, M, Di Bartolo, BA, Thomas, SR, Adams, LA, Kavurma, MM |
| المصدر: | urn:ISSN:2045-2322 ; Scientific Reports, 7, 1, 1898 |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2017 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | 3101 Biochemistry and Cell Biology, 31 Biological Sciences, Cardiovascular, Obesity, Hepatitis, Women's Health, Nutrition, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Diabetes, Liver Disease, Heart Disease, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, 3 Good Health and Well Being, Adult, Aged, Animals, Biomarkers, Body Weights and Measures, Diabetes Mellitus, Diet, High-Fat, Disease Models, Animal, Female, Gene Deletion, Glucose, Humans |
| الوصف: | Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail -/- mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | http://hdl.handle.net/1959.4/unsworks_54059 |
| DOI: | 10.1038/s41598-017-01721-4 |
| الاتاحة: | http://hdl.handle.net/1959.4/unsworks_54059 https://doi.org/10.1038/s41598-017-01721-4 |
| Rights: | open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.85A13BDA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-017-01721-4 |
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