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Mantena 2009 Biochem J

From Bioblast
Publications in the MiPMap
Mantena SK, Vaughn Jr DP, Andringa KK, Eccleston HB, King AL, Abrams GA, Doeller JE, Kraus DW, Darley-Usmar V, Bailey SM (2009) High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J 417:183โ€“93.

ยป PMID: 18752470 Open Access; pdf

Mantena SK, Vaughn Jr DP, Andringa KK, Eccleston HB, King AL, Abrams GA, Doeller JE, Kraus DW, Darley-Usmar V, Bailey SM (2009) Biochem J

Abstract: 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). Here in 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 approximately 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. โ€ข Keywords: Cytochrome c oxidase, Hypoxia, Liver, Mitochondria, Nitric oxide, Non-alcoholic steatohepatitis

โ€ข O2k-Network Lab: US AL Birmingham Kraus DW


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 

Stress:Ischemia-reperfusion, Mitochondrial disease  Organism: Mouse  Tissue;cell: Liver  Preparation: Intact cells 

Regulation: Aerobic glycolysis, ADP, Inhibitor  Coupling state: OXPHOS 

HRR: Oxygraph-2k