Abstract
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that regulates cellular redox potential. In this study, we demonstrate that macrophage G6PD plays an important role in the modulation of proinflammatory responses and oxidative stress. The G6PD levels in macrophages in the adipose tissue of obese animals were elevated, and G6PD mRNA levels positively correlated with those of proinflammatory genes. Lipopolysaccharide (LPS) and free fatty acids, which initiate proinflammatory signals, stimulated macrophage G6PD. Overexpression of macrophage G6PD potentiated the expression of proinflammatory and pro-oxidative genes responsible for the aggravation of insulin sensitivity in adipocytes. In contrast, when macrophage G6PD was inhibited or suppressed via chemical inhibitors or small interfering RNA (siRNA), respectively, basal and LPS-induced proinflammatory gene expression was attenuated. Furthermore, macrophage G6PD increased activation of the p38 mitogen-activated protein kinase (MAPK) and NF-κB pathways, which may lead to a vicious cycle of oxidative stress and proinflammatory cascade. Together, these data suggest that an abnormal increase of G6PD in macrophages promotes oxidative stress and inflammatory responses in the adipose tissue of obese animals.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / metabolism
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Adipose Tissue / enzymology
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Adipose Tissue / metabolism
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Animals
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Cell Line
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Chemokine CCL2 / biosynthesis
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Fatty Acids, Nonesterified / metabolism
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Female
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Glucosephosphate Dehydrogenase / antagonists & inhibitors
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Glucosephosphate Dehydrogenase / genetics
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Glucosephosphate Dehydrogenase / metabolism*
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Green Fluorescent Proteins / genetics
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Humans
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Inflammation / immunology
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Interleukin-1beta / biosynthesis
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Interleukin-6 / biosynthesis
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Lipopolysaccharides / pharmacology
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Macrophages / enzymology
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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NADP / pharmacology
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NF-kappa B / metabolism
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Obesity
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Oxidation-Reduction
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Oxidative Stress*
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RNA Interference
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RNA, Messenger / analysis
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RNA, Small Interfering
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Reactive Nitrogen Species / metabolism
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Reactive Oxygen Species / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Ccl2 protein, mouse
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Chemokine CCL2
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Fatty Acids, Nonesterified
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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RNA, Messenger
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RNA, Small Interfering
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Reactive Nitrogen Species
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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NADP
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Glucosephosphate Dehydrogenase
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p38 Mitogen-Activated Protein Kinases