High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo
| العنوان: | High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo |
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| المؤلفون: | Shannon M. Bailey, Heather B. Eccleston, David W. Kraus, Victor M. Darley-Usmar, Sudheer K. Mantena, Jeannette E. Doeller, Kelly K. Andringa, Adrienne L. King, Denty Paul Vaughn, Gary A. Abrams |
| المصدر: | Biochemical Journal |
| بيانات النشر: | Portland Press Ltd., 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, Bioenergetics, Nitric Oxide Synthase Type II, Mitochondria, Liver, Mitochondrion, medicine.disease_cause, Biochemistry, JC-1, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol carbo-cyanine iodide, chemistry.chemical_compound, Mice, 0302 clinical medicine, HFD, high fat diet, cytochrome c oxidase, 3-NT, 3-nitrotyrosine, Hypoxia, Membrane Potential, Mitochondrial, 0303 health sciences, Fatty liver, CYP2E1, cytochrome P450 2E1, Cytochrome P-450 CYP2E1, 3. Good health, mitochondria, FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 030220 oncology & carcinogenesis, iNOS, inducible nitric oxide synthase, non-alcoholic steatohepatitis, RCR, respiratory control ratio, Research Article, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, Cellular respiration, NASH, non-alcoholic steatohepatitis, Cell Respiration, Biology, liver, Nitric Oxide, Nitric oxide, PAPA NONOate, 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazino), DAB, diaminobenzidine, RNS, reactive nitrogen species, Mitochondrial Proteins, 03 medical and health sciences, ROS, reactive oxygen species, Internal medicine, medicine, Animals, Molecular Biology, Reactive nitrogen species, 030304 developmental biology, nutritional and metabolic diseases, Cell Biology, medicine.disease, Dietary Fats, Fatty Liver, Mice, Inbred C57BL, Oxidative Stress, Endocrinology, chemistry, Tyrosine, Steatohepatitis, Oxidative stress, DAPI, 4′,6-diamidino-2-phenylindole |
| الوصف: | NAFLD (non-alcoholic fatty liver disease), associated with obesity and the cardiometabolic syndrome, is an important medical problem affecting up to 20% of western populations. Evidence indicates that mitochondrial dysfunction plays a critical role in NAFLD initiation and progression to the more serious condition of NASH (non-alcoholic steatohepatitis). Herein we hypothesize that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species). To test this concept, C57BL/6 mice were pair-fed a control diet and HFD containing 35% and 71% total calories (1 cal≈4.184 J) from fat respectively, for 8 or 16 weeks and liver hypoxia, mitochondrial bioenergetics, NO (nitric oxide)-dependent control of respiration, and 3-NT (3-nitrotyrosine), a marker of protein modification by RNS, were examined. Feeding a HFD for 16 weeks induced NASH-like pathology accompanied by elevated triacylglycerols, increased CYP2E1 (cytochrome P450 2E1) and iNOS (inducible nitric oxide synthase) protein, and significantly enhanced hypoxia in the pericentral region of the liver. Mitochondria from the HFD group showed increased sensitivity to NO-dependent inhibition of respiration compared with controls. In addition, accumulation of 3-NT paralleled the hypoxia gradient in vivo and 3-NT levels were increased in mitochondrial proteins. Liver mitochondria from mice fed the HFD for 16 weeks exhibited depressed state 3 respiration, uncoupled respiration, cytochrome c oxidase activity, and mitochondrial membrane potential. These findings indicate that chronic exposure to a HFD negatively affects the bioenergetics of liver mitochondria and this probably contributes to hypoxic stress and deleterious NO-dependent modification of mitochondrial proteins. |
| اللغة: | English |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a8ad50b2a6a6f4a72113fc86354941bTest http://europepmc.org/articles/PMC2637578Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8a8ad50b2a6a6f4a72113fc86354941b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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