The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in obesity

ABSTRACT Obesity is closely associated with metabolic diseases including type 2 diabetes. One hallmark characteristics of obesity is chronic inflammation that is coordinately controlled by complex signaling networks in adipose tissues. Compelling evidence indicates that reactive oxygen species (ROS) and its related signaling pathways play crucial roles in the progression of chronic inflammation in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that utilizes the glucoses to generate molecular building blocks and reducing equivalents in the form of NADPH. In particular, NADPH acts as one of the key modulators in the control of ROS through providing an electron for both ROS generation and scavenging. Recently, we have reported that glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the PPP, is implicated in adipose tissue inflammation and systemic insulin resistance in obesity. Mechanistically, G6PD potentiates generation of ROS that augments pro-inflammatory responses in adipose tissue macrophages, leading to systemic insulin resistance. Here, we provide an overview of cell type- specific roles of G6PD in the regulation of ROS balance as well as additional details on the significance of G6PD that contributes to pro-oxidant NADPH generation in obesity-related chronic inflammation and insulin resistance.

[1]  Ji‐Won Kim,et al.  Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity , 2016, Diabetes.

[2]  M. Serrano,et al.  G6PD protects from oxidative damage and improves healthspan in mice , 2016, Nature Communications.

[3]  S. Gupte,et al.  Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[4]  R. Andriantsitohaina,et al.  Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View , 2014, Oxidative medicine and cellular longevity.

[5]  L. Luzzatto,et al.  Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells. , 2014, Blood.

[6]  J. B. Kim,et al.  Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity , 2014, Molecules and cells.

[7]  T. Mak,et al.  Modulation of oxidative stress as an anticancer strategy , 2013, Nature Reviews Drug Discovery.

[8]  Dorothy D. Sears,et al.  Macrophage Glucose-6-Phosphate Dehydrogenase Stimulates Proinflammatory Responses with Oxidative Stress , 2013, Molecular and Cellular Biology.

[9]  F. Recchia,et al.  Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease. , 2013, American journal of physiology. Heart and circulatory physiology.

[10]  S. Matalon,et al.  Post-exposure antioxidant treatment in rats decreases airway hyperplasia and hyperreactivity due to chlorine inhalation. , 2012, American journal of respiratory cell and molecular biology.

[11]  R. Simmen,et al.  Cytosolic Malic Enzyme 1 (ME1) Mediates High Fat Diet-Induced Adiposity, Endocrine Profile, and Gastrointestinal Tract Proliferation-Associated Biomarkers in Male Mice , 2012, PloS one.

[12]  R. Stanton.  Glucose‐6‐phosphate dehydrogenase, NADPH, and cell survival , 2012, IUBMB life.

[13]  W. Seeger,et al.  Hypoxia induces Kv channel current inhibition by increased NADPH oxidase-derived reactive oxygen species. , 2012, Free radical biology & medicine.

[14]  Carey N Lumeng,et al.  Inflammatory links between obesity and metabolic disease. , 2011, The Journal of clinical investigation.

[15]  P. Scherer,et al.  Adipose tissue remodeling and obesity. , 2011, The Journal of clinical investigation.

[16]  T. Kanamoto,et al.  Platelet-derived growth factor receptor alpha is associated with oxidative stress-induced retinal cell death. , 2011, Current Eye Research.

[17]  Dalong Zhu,et al.  Apocynin Improves Insulin Resistance through Suppressing Inflammation in High-Fat Diet-Induced Obese Mice , 2011, Mediators of inflammation.

[18]  Ji‐Won Kim,et al.  G6PD up-regulation promotes pancreatic beta-cell dysfunction. , 2011, Endocrinology.

[19]  T. Zhou,et al.  The role of lipid peroxidation products and oxidative stress in activation of the canonical wingless-type MMTV integration site (WNT) pathway in a rat model of diabetic retinopathy , 2010, Diabetologia.

[20]  Jonathan R. Brestoff,et al.  Downregulation of Adipose Glutathione S-Transferase A4 Leads to Increased Protein Carbonylation, Oxidative Stress, and Mitochondrial Dysfunction , 2010, Diabetes.

[21]  J. Carballido,et al.  Analgesic efficacy of zoledronic acid and its effect on functional status of prostate cancer patients with metastasis , 2008, Patient preference and adherence.

[22]  J. Olefsky,et al.  Inflammation and insulin resistance , 2008, FEBS letters.

[23]  Jiyoung Park,et al.  New evaluations of redox regulating system in adipose tissue of obesity. , 2007, Diabetes research and clinical practice.

[24]  F. Recchia,et al.  Upregulation of glucose-6-phosphate dehydrogenase and NAD(P)H oxidase activity increases oxidative stress in failing human heart. , 2007, Journal of cardiac failure.

[25]  M. Collu,et al.  Production of Inflammatory Molecules in Peripheral Blood Mononuclear Cells from Severely Glucose-6-Phosphate Dehydrogenase-Deficient Subjects , 2007, Journal of Vascular Research.

[26]  Jiyoung Park,et al.  Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals , 2006, Diabetes.

[27]  F. Recchia,et al.  Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart. , 2006, Journal of molecular and cellular cardiology.

[28]  E. Lander,et al.  Reactive oxygen species have a causal role in multiple forms of insulin resistance , 2006, Nature.

[29]  Jiyoung Park,et al.  Overexpression of Glucose-6-Phosphate Dehydrogenase Is Associated with Lipid Dysregulation and Insulin Resistance in Obesity , 2005, Molecular and Cellular Biology.

[30]  Morihiro Matsuda,et al.  Increased oxidative stress in obesity and its impact on metabolic syndrome. , 2004, The Journal of clinical investigation.

[31]  T. Huh,et al.  Cytosolic NADP+-dependent Isocitrate Dehydrogenase Plays a Key Role in Lipid Metabolism* , 2004, Journal of Biological Chemistry.

[32]  J. López-Barneo,et al.  Induction of the glucose‐6‐phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells , 2004, FEBS letters.

[33]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[34]  Z. Bloomgarden,et al.  Inflammation and insulin resistance. , 2003, Diabetes care.

[35]  E. Benjamin,et al.  Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[36]  W. Ebstein.  Invited comment on W. Ebstein: On the therapy of diabetes mellitus, in particular on the application of sodium salicylate. , 2002, Journal of molecular medicine.

[37]  S. Shoelson.  JMM – Past and Present , 2002, Journal of Molecular Medicine.

[38]  S. Olusi.  Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotectic enzymes in humans , 2002, International Journal of Obesity.

[39]  C. Riganti,et al.  Crocidolite asbestos inhibits pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human lung epithelial cells. , 2002, Free radical biology & medicine.

[40]  R. Dringen,et al.  Metabolism and functions of glutathione in brain , 2000, Progress in Neurobiology.

[41]  R. L. Russell,et al.  Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease. , 1999, Archives of biochemistry and biophysics.

[42]  A. A. Leite,et al.  Erythrocyte glucose-6-phosphate dehydrogenase activity assay and affinity for its substrate under "physiological" conditions. , 1998, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[43]  J. Hothersall,et al.  Inhibition of NADPH supply by 6‐aminonicotinamide: effect on glutathione, nitric oxide and superoxide in J774 cells , 1998, FEBS letters.

[44]  M. Nedergaard,et al.  Vitamin E, Ascorbate, Glutathione, Glutathicne Disulfide, and Enzymes of Glutathione Metabolism in Cultures of Chick Astrocytes and Neurons: Evidence that Astrocytes Play an Important Role in Antioxidative Processes in the Brain , 1994, Journal of neurochemistry.

[45]  J. Lai,et al.  Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons , 1989, Brain Research.

[46]  Dhiren P. Shah,et al.  ON OXIDATIVE STRESS AND DIABETIC COMPLICATIONS , 2013 .

[47]  K. Krause,et al.  The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. , 2007, Physiological reviews.

[48]  A. M. Palmer,et al.  The activity of the pentose phosphate pathway is increased in response to oxidative stress in Alzheimer's disease , 1999, Journal of Neural Transmission.

[49]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.