Difference between revisions of "Anderson 2009 J Clin Invest"
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|journal=J Clin Invest | |journal=J Clin Invest | ||
|abstract=High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H<sub>2</sub>O<sub>2</sub>-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H<sub>2</sub>O<sub>2</sub>emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial H<sub>2</sub>O<sub>2</sub> emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity. | |abstract=High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H<sub>2</sub>O<sub>2</sub>-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H<sub>2</sub>O<sub>2</sub>emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial H<sub>2</sub>O<sub>2</sub> emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity. | ||
|keywords=Miotochondrial bioenergetics,ย Insulin resistance, Transgenic mice, Stress sensitive signalling kinases, NF-ฮบB pathway, Mitochondrial H<sub>2</sub>O<sub>2</sub>-emitting potential | |keywords=Miotochondrial bioenergetics,ย Insulin resistance, Transgenic mice, Stress sensitive signalling kinases, NF-ฮบB pathway, Mitochondrial H<sub>2</sub>O<sub>2</sub>-emitting potential, Amplex Red | ||
|mipnetlab=US NC Greenville Neufer PD, US NC Greenville Anderson EJ, US TN Nashville Wasserman DH, CA Antigonish Kane DA, US NC Greenville East Carolina Univ | |mipnetlab=US NC Greenville Neufer PD, US NC Greenville Anderson EJ, US TN Nashville Wasserman DH, CA Antigonish Kane DA, US NC Greenville East Carolina Univ | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Respiration | ||
|organism=Human, Mouse, Rat | |organism=Human, Mouse, Rat | ||
| | |tissues=Skeletal muscle | ||
|preparations=Permeabilized tissue | |||
|enzymes=Complex I, Complex II; Succinate Dehydrogenase, Uncoupling protein | |enzymes=Complex I, Complex II; Succinate Dehydrogenase, Uncoupling protein | ||
|injuries=RONS; Oxidative Stress | |||
|diseases=Diabetes | |||
|topics=Fatty Acid | |topics=Fatty Acid | ||
|couplingstates=OXPHOS, ETS | |||
|instruments=Oxygraph-2k | |||
}} | }} | ||
Revision as of 12:36, 24 January 2014
| Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin C-T, Price JW, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119: 573-581. |
Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) J Clin Invest
Abstract: High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the H2O2-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial H2O2emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial H2O2 emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity. โข Keywords: Miotochondrial bioenergetics, Insulin resistance, Transgenic mice, Stress sensitive signalling kinases, NF-ฮบB pathway, Mitochondrial H2O2-emitting potential, Amplex Red
โข O2k-Network Lab: US NC Greenville Neufer PD, US NC Greenville Anderson EJ, US TN Nashville Wasserman DH, CA Antigonish Kane DA, US NC Greenville East Carolina Univ
Labels: MiParea: Respiration
Pathology: Diabetes
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Organism: Human, Mouse, Rat
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Enzyme: Complex I, Complex II; Succinate Dehydrogenase"Complex II; Succinate Dehydrogenase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Uncoupling protein
Regulation: Fatty Acid"Fatty Acid" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
Coupling state: OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
