| NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes. | |
| | |
MedLine Citation:
|
PMID: 22287546 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
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 (250μM) in either 5mM or 25mM 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 NOX 4 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 (PPP) activity, increased with glucose but not palmitate, and decreased with DHA exposure. Inhibition of PPP 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. |
| | |
Authors:
|
Chang Yeop Han; Tomio Umemoto; Mohamed Omer; Laura J Den Hartigh; Tsuyoshi Chiba; Renee Leboeuf; Carolyn L Buller; Ian R Sweet; Subramaniam Pennathur; E Dale Abel; Alan Chait |
Related Documents
:
|
21697546 - Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using... 2680966 - Nutritional deficiencies in chronic pancreatitis. 17312466 - Evaluation of pancreatic endocrine and exocrine function in patients with autoimmune pa... 7398096 - Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabe... 22054146 - Epidemiology and economic impact of obesity and type 2 diabetes. 2111786 - Human antral damage induced by alcohol is potentiated by enprostil. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-27 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-30 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Washington, United States; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Insights into hemoglobin assembly through in vivo mutagenesis of alpha-hemoglobin stabilizing protei...
Next Document: PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma.