Cited by 187Adipokines, Inflammation, and Metabolic DiseasesRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

NADPH Oxidase-derived Reactive Oxygen Species Increases Expression of Monocyte Chemotactic Factor Genes in Cultured Adipocytes

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Han, Chang Yeop, Umemoto, Tomio, Omer, Mohamed, Den Hartigh, Laura J., Chiba, Tsuyoshi, LeBoeuf, Renee, Buller, Carolyn L., Sweet, Ian R. +3 more·2012·Journal of Biological Chemistry

Abstract

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 μM) in either 5 or 25 mM 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.

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Crossref · 10.1074/jbc.m111.304998

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  • By suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.

    “Thus, by suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.12–20”
  • In obesity, excess free fatty acids increase NOX-mediated ROS generation.

    “In obesity, the excess of FFAs increases NOX-mediated ROS generation.”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [60]

  • Increased ROS in adipocytes exposed to excess free fatty acids does not depend on enhanced mitochondrial flux, but on high levels of TNFα and ER stress as well as upregulation of NOX enzymes.

    “Recently, it has been demonstrated that increased ROS in adipocytes exposed to an excess of FFAs does not depend on enhanced mitochondrial flux, but on high levels of TNFα and ER stress as well as the upregulation of aforementioned NOX enzymes ([8](#B8), [60](#B60)).”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [60]

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Authors
Han, C. Y., Umemoto, T., Omer, M., Den Hartigh, L. J., Chiba, T., LeBoeuf, R., Buller, C. L., Sweet, I. R., Pennathur, S., Abel, E. D., & Chait, A.
Affiliations
  • University of Washington (US)
  • University of Michigan (US)
  • University of Utah (US)
Corresponding author
Chait, Alan
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2012-03
Volume
287
Issue
13
Pages
10379-10393
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2017814607
Cited by
187
References
59
Citations by year
2026: 4 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 16 · 2020: 16 · 2019: 15 · 2018: 17 · 2017: 15 · 2016: 18 · 2015: 6 · 2014: 12 · 2013: 15 · 2012: 9
FWCI
10.02
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R56HL094352, HL-094352, R01HL094352, R01HL098227)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R24DK082841, DK-082841, DK092065, DK089503, DK-17047, R01DK092065, P30DK020572, P30DK035816, P30DK017047, P30DK089503)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
NADPH oxidase, NOX4, reactive oxygen species, adipocytes, monocyte chemotactic factor, MCP-1, docosahexaenoic acid, palmitate, glucose, pentose phosphate pathway, NADPH, lipid rafts, mitochondrial electron transport chain, insulin resistance, adipose tissue inflammation, 3T3-L1 adipocytes
MeSH terms
NADPH Oxidase 4, Animals, Docosahexaenoic Acids, Enzyme Inhibitors, Glucose, Mitochondria, Pentose Phosphate Pathway, Sweetening Agents, Reactive Oxygen Species, Adipocytes, Monocyte Chemoattractant Proteins, NADPH Oxidases, Palmitic Acid, Protein Transport, Membrane Microdomains, 3T3-L1 Cells, Mice

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