|
 |
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print May 9, 2007
J. Lipid Res., doi:10.1194/jlr.R700007-JLR200
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115
Corresponding Author: ghotamis{at}hsph.harvard.edu
In the context of obesity and its related maladies, the adipocyte plays a central role in the balance, or imbalance, of metabolic homeostasis. An obese, hypertrophic adipocyte is challenged by many insults including surplus energy, inflammation, insulin resistance, and considerable stress to various organelles. The endoplasmic reticulum (ER) is one such vital organelle that demonstrates significant signs of stress and dysfunction in obesity and insulin resistance. Under normal conditions, the ER must function in the unique and trying environment of the adipocyte, adapting to meet the demands of increased protein synthesis and secretion, energy storage in the form of triglyceride droplet formation, and nutrient sensing, particular to the differentiated fat cell. When nutrients are in pathological excess, the ER is overwhelmed and the unfolded protein response (UPR) is activated. Remarkably, the consequences of UPR activation have been causally linked to the development of insulin resistance through a multitude of possible mechanisms including JNK activation, inflammation, and oxidative stress. This review will focus on the function of the endoplasmic reticulum under normal conditions in the adipocyte, and the pathological effects of a stressed ER contributing to adipocyte dysfunction and a thwarted metabolic homeostasis.
Revised on May 9, 2007
Accepted on May 9, 2007
Adipocyte stress: The endoplasmic reticulum and metabolic disease
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Boden, M. Silviera, B. Smith, P. Cheung, and C. Homko Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress J. Clin. Endocrinol. Metab., January 1, 2010; 95(1): 349 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ye, D. Y. Jung, J. Y. Jun, J. Li, S. Luo, H. J. Ko, J. K. Kim, and A. S. Lee Grp78 Heterozygosity Promotes Adaptive Unfolded Protein Response and Attenuates Diet-Induced Obesity and Insulin Resistance Diabetes, January 1, 2010; 59(1): 6 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basseri, S. Lhotak, A. M. Sharma, and R. C. Austin The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response J. Lipid Res., December 1, 2009; 50(12): 2486 - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jiang, Z. Wang, J.-J. Riethoven, Y. Xia, J. Miner, and M. Fromm Conjugated Linoleic Acid Activates AMP-Activated Protein Kinase and Reduces Adiposity More Effectively When Used with Metformin in Mice J. Nutr., December 1, 2009; 139(12): 2244 - 2251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Liu, S. Y. Cao, T. Hong, J. Han, Z. Liu, and W. Cao Insulin Is a Stronger Inducer of Insulin Resistance than Hyperglycemia in Mice with Type 1 Diabetes Mellitus (T1DM) J. Biol. Chem., October 2, 2009; 284(40): 27090 - 27100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Liu, T. Hong, G.-B. Wen, J. Han, D. Zuo, Z. Liu, and W. Cao Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E898 - E906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Pauw, S. Tejerina, M. Raes, J. Keijer, and T. Arnould Mitochondrial (Dys)function in Adipocyte (De)differentiation and Systemic Metabolic Alterations Am. J. Pathol., September 1, 2009; 175(3): 927 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Lefterova, S. E. Mullican, T. Tomaru, M. Qatanani, M. Schupp, and M. A. Lazar Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression Diabetes, August 1, 2009; 58(8): 1879 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bluher, N. Bashan, I. Shai, I. Harman-Boehm, T. Tarnovscki, E. Avinaoch, M. Stumvoll, A. Dietrich, N. Kloting, and A. Rudich Activated Ask1-MKK4-p38MAPK/JNK Stress Signaling Pathway in Human Omental Fat Tissue May Link Macrophage Infiltration to Whole-Body Insulin Sensitivity J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2507 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sharkey, D. S. Gardner, H. P. Fainberg, S. Sebert, P. Bos, V. Wilson, R. Bell, M. E. Symonds, and H. Budge Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring FASEB J, May 1, 2009; 23(5): 1314 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Du and J. Ding Insulin Regulates TRB3 and Other Stress-Responsive Gene Expression through Induction of C/EBP{beta} Mol. Endocrinol., April 1, 2009; 23(4): 475 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. G. Zhou, M. Zhou, F. F. Hou, and X. Peng Asymmetrical dimethylarginine triggers lipolysis and inflammatory response via induction of endoplasmic reticulum stress in cultured adipocytes Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E869 - E878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Attie and P. E. Scherer Adipocyte metabolism and obesity J. Lipid Res., April 1, 2009; 50(Supplement): S395 - S399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boden Endoplasmic Reticulum Stress: Another Link Between Obesity and Insulin Resistance/Inflammation? Diabetes, March 1, 2009; 58(3): 518 - 519. [Full Text] [PDF]
|
|
|
|
|
|
M. F. Gregor, L. Yang, E. Fabbrini, B. S. Mohammed, J. C. Eagon, G. S. Hotamisligil, and S. Klein Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss Diabetes, March 1, 2009; 58(3): 693 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Delibegovic, D. Zimmer, C. Kauffman, K. Rak, E.-G. Hong, Y.-R. Cho, J. K. Kim, B. B. Kahn, B. G. Neel, and K. K. Bence Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress Diabetes, March 1, 2009; 58(3): 590 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Orasanu and J. Plutzky The pathologic continuum of diabetic vascular disease. J. Am. Coll. Cardiol., February 3, 2009; 53(5 Suppl): S35 - S42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kennedy, A. Overman, K. LaPoint, R. Hopkins, T. West, C.-C. Chuang, K. Martinez, D. Bell, and M. McIntosh Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol J. Lipid Res., February 1, 2009; 50(2): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liu, L. Zhou, A. Xu, K. S. L. Lam, M. D. Wetzel, R. Xiang, J. Zhang, X. Xin, L. Q. Dong, and F. Liu From the Cover: A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization PNAS, November 25, 2008; 105(47): 18302 - 18307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Sharma, S. K. Das, A. K. Mondal, O. G. Hackney, W. S. Chu, P. A. Kern, N. Rasouli, H. J. Spencer, A. Yao-Borengasser, and S. C. Elbein Endoplasmic Reticulum Stress Markers Are Associated with Obesity in Nondiabetic Subjects J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4532 - 4541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Prentki and S. R. M. Madiraju Glycerolipid Metabolism and Signaling in Health and Disease Endocr. Rev., October 1, 2008; 29(6): 647 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Lira, A. K. Loomis, S. A. Paciga, D. B. Lloyd, and J. F. Thompson Expression of CETP and of splice variants induces the same level of ER stress despite secretion efficiency differences J. Lipid Res., September 1, 2008; 49(9): 1955 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boden, X. Duan, C. Homko, E. J. Molina, W. Song, O. Perez, P. Cheung, and S. Merali Increase in Endoplasmic Reticulum Stress-Related Proteins and Genes in Adipose Tissue of Obese, Insulin-Resistant Individuals Diabetes, September 1, 2008; 57(9): 2438 - 2444. [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]
|
|
|
|
 |
|
 S. de Ferranti and D. Mozaffarian The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences Clin. Chem., June 1, 2008; 54(6): 945 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Eizirik, A. K. Cardozo, and M. Cnop The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus Endocr. Rev., February 1, 2008; 29(1): 42 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. LaRosa, J.-J. M. Riethoven, H. Chen, Y. Xia, Y. Zhou, M. Chen, J. Miner, and M. E. Fromm Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes Physiol Genomics, November 14, 2007; 31(3): 544 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mozaffarian Free fatty acids, cardiovascular mortality, and cardiometabolic stress Eur. Heart J., November 2, 2007; 28(22): 2699 - 2700. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |