| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 280, Issue 6, 4617-4626, February 11, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
**¶¶
From the
Departments of Cell Biology, ¶Pathology, and **Medicine, and the Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461, the Departments of Medicine and Physiology and Banting and Best Diabetes Center, University of Toronto, Toronto, Ontario M5G 1X5, Canada, the ||ABR-Affinity BioReagents, Golden, Colorado 80403, and the Pacific Northwest Research Institute and Department of Pharmacology, University of Washington, Seattle, Washington 98122
Hyperglycemia is a major independent risk factor for diabetic macrovascular disease. The consequences of exposure of endothelial cells to hyperglycemia are well established. However, little is known about how adipocytes respond to both acute as well as chronic exposure to physiological levels of hyperglycemia. Here, we analyze adipocytes exposed to hyperglycemia both in vitro as well as in vivo. Comparing cells differentiated at 4 mM to cells differentiated at 25 mM glucose (the standard differentiation protocol) reveals severe insulin resistance in cells exposed to 25 mM glucose. A global assessment of transcriptional changes shows an up-regulation of a number of mitochondrial proteins. Exposure to hyperglycemia is associated with a significant induction of reactive oxygen species (ROS), both in vitro as well as in vivo in adipocytes isolated from streptozotocin-treated hyperglycemic mice. Furthermore, hyperglycemia for a few hours in a clamped setting will trigger the induction of a pro-inflammatory response in adipose tissue from rats that can effectively be reduced by co-infusion of N-acetylcysteine (NAC). ROS levels in 3T3-L1 adipocytes can be reduced significantly with pharmacological agents that lower the mitochondrial membrane potential, or by overexpression of uncoupling protein 1 or superoxide dismutase. In parallel with ROS, interleukin-6 secretion from adipocytes is significantly reduced. On the other hand, treatments that lead to a hyperpolarization of the mitochondrial membrane, such as overexpression of the mitochondrial dicarboxylate carrier result in increased ROS formation and decreased insulin sensitivity, even under normoglycemic conditions. Combined, these results highlight the importance ROS production in adipocytes and the associated insulin resistance and inflammatory response.
Received for publication, October 19, 2004
* This work was supported by Grant R01-HL-073163-01 (to Y. L.), an American Diabetes Association Medical Scientist Training grant (to A. H. B.), National Institutes of Health Medical Scientist Training Grant T32-GM07288 (to P. I. and M. W. R.), National Institutes of Health National Research Service Award DK61228 (to T. P. C.), Canadian Institutes of Health Research Grant MOP-38009 (to I. G. F.), National Institutes of Health Grants P01-AG021654 (to N. B. and M. B.), 1R01-DK55758 (to P. E. S.), and Juvenile Diabetes Research Foundation Award 1-2001-780 (to P. E. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶¶ To whom correspondence should be addressed. Tel.: 718-430-2928; Fax: 718-430-8574; E-mail: scherer{at}aecom.yu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. S. Lee, A Y. Kim, J. W. Choi, M. Kim, S. Yasue, H. J. Son, H. Masuzaki, K. S. Park, and J. B. Kim Dysregulation of Adipose Glutathione Peroxidase 3 in Obesity Contributes to Local and Systemic Oxidative Stress Mol. Endocrinol., September 1, 2008; 22(9): 2176 - 2189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Peterson, G. Drummond, D. H. Kim, M. Li, A. L. Kruger, S. Ikehara, and N. G. Abraham L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice J. Lipid Res., August 1, 2008; 49(8): 1658 - 1669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kumashiro, Y. Tamura, T. Uchida, T. Ogihara, Y. Fujitani, T. Hirose, H. Mochizuki, R. Kawamori, and H. Watada Impact of Oxidative Stress and Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1{alpha} in Hepatic Insulin Resistance Diabetes, August 1, 2008; 57(8): 2083 - 2091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yu, S.-S. Sheu, J. L. Robotham, and Y. Yoon Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species Cardiovasc Res, July 15, 2008; 79(2): 341 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Copeland, J. W. Bullen, and G. W. Hart Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E17 - E28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-S. Gauthier, H. Miyoshi, S. C. Souza, J. M. Cacicedo, A. K. Saha, A. S. Greenberg, and N. B. Ruderman AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte: POTENTIAL MECHANISM AND PHYSIOLOGICAL RELEVANCE J. Biol. Chem., June 13, 2008; 283(24): 16514 - 16524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Kim, A. P. Burgess, M. Li, P. L. Tsenovoy, F. Addabbo, J. A. McClung, N. Puri, and N. G. Abraham Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis Factor-{alpha} and Interleukin-6 in Zucker Rats and Reduce Adipogenesis in Human Mesenchymal Stem Cells J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 833 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Li, D. H. Kim, P. L. Tsenovoy, S. J. Peterson, R. Rezzani, L. F. Rodella, W. S. Aronow, S. Ikehara, and N. G. Abraham Treatment of Obese Diabetic Mice With a Heme Oxygenase Inducer Reduces Visceral and Subcutaneous Adiposity, Increases Adiponectin Levels, and Improves Insulin Sensitivity and Glucose Tolerance Diabetes, June 1, 2008; 57(6): 1526 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, C. Jiang, G. Xu, N. Wang, Y. Zhu, C. Tang, and X. Wang Homocysteine Upregulates Resistin Production From Adipocytes In Vivo and In Vitro Diabetes, April 1, 2008; 57(4): 817 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. V. de Cavanagh, L. Ferder, J. E. Toblli, B. Piotrkowski, I. Stella, C. G. Fraga, and F. Inserra Renal mitochondrial impairment is attenuated by AT1 blockade in experimental Type I diabetes Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H456 - H465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nagai, J. W. Brock, M. Blatnik, J. E. Baatz, J. Bethard, M. D. Walla, S. R. Thorpe, J. W. Baynes, and N. Frizzell Succination of Protein Thiols during Adipocyte Maturation: A BIOMARKER OF MITOCHONDRIAL STRESS J. Biol. Chem., November 23, 2007; 282(47): 34219 - 34228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rao, Z. H. Huang, and T. Mazzone Angiotensin II Regulates Adipocyte Apolipoprotein E Expression J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4366 - 4372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-W. Yan, Q. Yang, N. Mody, T. E. Graham, C.-H. Hsu, Z. Xu, N. E. Houstis, B. B. Kahn, and E. D. Rosen The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance Diabetes, October 1, 2007; 56(10): 2533 - 2540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Huang, L.-Y. Chuang, J.-Y. Guh, Y.-J. Huang, and M.-S. Hsu Antioxidants attenuate high glucose-induced hypertrophic growth in renal tubular epithelial cells Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1072 - F1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Y. Han, S. Subramanian, C. K. Chan, M. Omer, T. Chiba, T. N. Wight, and A. Chait Adipocyte-Derived Serum Amyloid A3 and Hyaluronan Play a Role in Monocyte Recruitment and Adhesion Diabetes, September 1, 2007; 56(9): 2260 - 2273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Khazen, E. Distel, M. Collinet, V. E. Chaves, J.-P. M'Bika, C. Chany, A. Achour, C. Benelli, and C. Forest Acute and Selective Inhibition of Adipocyte Glyceroneogenesis and Cytosolic Phosphoenolpyruvate Carboxykinase by Interferon {gamma} Endocrinology, August 1, 2007; 148(8): 4007 - 4014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. H. Huang, R. M. Luque, R. D. Kineman, and T. Mazzone Nutritional regulation of adipose tissue apolipoprotein E expression Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E203 - E209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Si, S. Palani, A. Jayaraman, and K. Lee Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism J. Lipid Res., April 1, 2007; 48(4): 826 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Grimsrud, M. J. Picklo Sr., T. J. Griffin, and D. A. Bernlohr Carbonylation of Adipose Proteins in Obesity and Insulin Resistance: Identification of Adipocyte Fatty Acid-binding Protein as a Cellular Target of 4-Hydroxynonenal Mol. Cell. Proteomics, April 1, 2007; 6(4): 624 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Meugnier, M. Faraj, S. Rome, G. Beauregard, A. Michaut, V. Pelloux, J.-L. Chiasson, M. Laville, K. Clement, H. Vidal, et al. Acute Hyperglycemia Induces a Global Downregulation of Gene Expression in Adipose Tissue and Skeletal Muscle of Healthy Subjects Diabetes, April 1, 2007; 56(4): 992 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Desruisseaux, Nagajyothi, M. E. Trujillo, H. B. Tanowitz, and P. E. Scherer Adipocyte, Adipose Tissue, and Infectious Disease Infect. Immun., March 1, 2007; 75(3): 1066 - 1078. [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Trujillo and P. E. Scherer Adipose Tissue-Derived Factors: Impact on Health and Disease Endocr. Rev., December 1, 2006; 27(7): 762 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Joseph, M. V. Jensen, O. Ilkayeva, F. Palmieri, C. Alarcon, C. J. Rhodes, and C. B. Newgard The Mitochondrial Citrate/Isocitrate Carrier Plays a Regulatory Role in Glucose-stimulated Insulin Secretion J. Biol. Chem., November 24, 2006; 281(47): 35624 - 35632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gyurko, C. C. Siqueira, N. Caldon, L. Gao, A. Kantarci, and T. E. Van Dyke Chronic Hyperglycemia Predisposes to Exaggerated Inflammatory Response and Leukocyte Dysfunction in Akita Mice J. Immunol., November 15, 2006; 177(10): 7250 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kamei, K. Tobe, R. Suzuki, M. Ohsugi, T. Watanabe, N. Kubota, N. Ohtsuka-Kowatari, K. Kumagai, K. Sakamoto, M. Kobayashi, et al. Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance J. Biol. Chem., September 8, 2006; 281(36): 26602 - 26614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Di Noia, S. Van Driesche, F. Palmieri, L.-M. Yang, S. Quan, A. I. Goodman, and N. G. Abraham Heme Oxygenase-1 Enhances Renal Mitochondrial Transport Carriers and Cytochrome c Oxidase Activity in Experimental Diabetes J. Biol. Chem., June 9, 2006; 281(23): 15687 - 15693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Scherer Adipose Tissue: From Lipid Storage Compartment to Endocrine Organ Diabetes, June 1, 2006; 55(6): 1537 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yu, J. L. Robotham, and Y. Yoon Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology PNAS, February 21, 2006; 103(8): 2653 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gorin, K. Block, J. Hernandez, B. Bhandari, B. Wagner, J. L. Barnes, and H. E. Abboud Nox4 NAD(P)H Oxidase Mediates Hypertrophy and Fibronectin Expression in the Diabetic Kidney J. Biol. Chem., November 25, 2005; 280(47): 39616 - 39626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cinti, G. Mitchell, G. Barbatelli, I. Murano, E. Ceresi, E. Faloia, S. Wang, M. Fortier, A. S. Greenberg, and M. S. Obin Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans J. Lipid Res., November 1, 2005; 46(11): 2347 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mizuarai, S. Miki, H. Araki, K. Takahashi, and H. Kotani Identification of Dicarboxylate Carrier Slc25a10 as Malate Transporter in de Novo Fatty Acid Synthesis J. Biol. Chem., September 16, 2005; 280(37): 32434 - 32441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Renstrom, J. Buren, and J. W. Eriksson Insulin Receptor Substrates-1 and -2 Are Both Depleted but via Different Mechanisms after Down-Regulation of Glucose Transport in Rat Adipocytes Endocrinology, July 1, 2005; 146(7): 3044 - 3051. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
