Journal article
NADPH Oxidase-derived Reactive Oxygen Species Increases Expression of Monocyte Chemotactic Factor Genes in Cultured Adipocytes
The Journal of biological chemistry, Vol.287(13), pp.10379-10393
03/23/2012
DOI: 10.1074/jbc.M111.304998
PMCID: PMC3322984
PMID: 22287546
Abstract
Background:
Excess nutrients induce adipose inflammation.
Results:
Excess glucose and palmitate generate ROS via NOX4 by a mechanism that involves the PPP and translocation of NOX4 into LRs, rather than by mitochondrial oxidation.
Conclusion:
NOX4 activates monocyte chemotactic factor expression.
Significance:
Understanding the source of ROS generation may lead to the development of new therapeutic targets for adipose tissue inflammation.
Excess glucose and free fatty acids delivered to adipose tissue causes local inflammation, which contributes to insulin resistance. Glucose and palmitate generate reactive oxygen species (ROS) in adipocytes, leading to monocyte chemotactic factor gene expression. Docosahexaenoate (DHA) has the opposite effect. In this study, we evaluated the potential sources of ROS in the presence of excess nutrients. Differentiated 3T3-L1 adipocytes were exposed to palmitate and DHA (250 μ
m
) in either 5 or 25 m
m
glucose to evaluate the relative roles of mitochondrial electron transport and NADPH oxidases (NOX) as sources of ROS. Excess glucose and palmitate did not increase mitochondrial oxidative phosphorylation. However, glucose exposure increased glycolysis. Of the NOX family members, only NOX4 was expressed in adipocytes. Moreover, its activity was increased by excess glucose and palmitate and decreased by DHA. Silencing NOX4 inhibited palmitate- and glucose-stimulated ROS generation and monocyte chemotactic factor gene expression. NADPH, a substrate for NOX, and pentose phosphate pathway activity increased with glucose but not palmitate and decreased with DHA exposure. Inhibition of the pentose phosphate pathway by glucose-6-phosphate dehydrogenase inhibitors and siRNA suppressed ROS generation and monocyte chemotactic factor gene expression induced by both glucose and palmitate. Finally, both high glucose and palmitate induced NOX4 translocation into lipid rafts, effects that were blocked by DHA. Excess glucose and palmitate generate ROS via NOX4 rather than by mitochondrial oxidation in cultured adipocytes. NOX4 is regulated by both NADPH generated in the PPP and translocation of NOX4 into lipid rafts, leading to expression of monocyte chemotactic factors.
Details
- Title: Subtitle
- NADPH Oxidase-derived Reactive Oxygen Species Increases Expression of Monocyte Chemotactic Factor Genes in Cultured Adipocytes
- Creators
- Chang Yeop Han - From theTomio Umemoto - From theMohamed Omer - From theLaura J Den Hartigh - From theTsuyoshi Chiba - From theRenee LeBoeuf - From theCarolyn L Buller - theIan R Sweet - From theSubramaniam Pennathur - theE. Dale Abel - theAlan Chait - From the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.287(13), pp.10379-10393
- DOI
- 10.1074/jbc.M111.304998
- PMID
- 22287546
- PMCID
- PMC3322984
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- DK092065; HL-094352; P30-DK-035816; DK-082841; DK-089503; DK-17047 / National Institutes of Health
- Alternative title
- NOX-derived ROS Increases Chemotactic Factors in Adipocytes
- Language
- English
- Date published
- 03/23/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025279502771
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