Journal article
Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
The Journal of clinical investigation, Vol.119(3), pp.573-581
03/02/2009
DOI: 10.1172/JCI37048
PMCID: PMC2648700
PMID: 19188683
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
2
O
2
-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
2
O
2
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
2
O
2
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.
Details
- Title: Subtitle
- Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
- Creators
- Ethan J Anderson - Metabolic Institute for the Study of Diabetes and ObesityMary E Lustig - Metabolic Institute for the Study of Diabetes and ObesityKristen E Boyle - Metabolic Institute for the Study of Diabetes and ObesityTracey L Woodlief - Metabolic Institute for the Study of Diabetes and ObesityDaniel A Kane - Metabolic Institute for the Study of Diabetes and ObesityChien-Te Lin - Metabolic Institute for the Study of Diabetes and ObesityJesse W Price - Metabolic Institute for the Study of Diabetes and ObesityLi Kang - Metabolic Institute for the Study of Diabetes and ObesityPeter S Rabinovitch - Metabolic Institute for the Study of Diabetes and ObesityHazel H Szeto - Metabolic Institute for the Study of Diabetes and ObesityJoseph A Houmard - Metabolic Institute for the Study of Diabetes and ObesityRonald N Cortright - Metabolic Institute for the Study of Diabetes and ObesityDavid H Wasserman - Metabolic Institute for the Study of Diabetes and ObesityP. Darrell Neufer - Metabolic Institute for the Study of Diabetes and Obesity
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.119(3), pp.573-581
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI37048
- PMID
- 19188683
- PMCID
- PMC2648700
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/02/2009
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology
- Record Identifier
- 9984065317102771
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