Endoplasmic reticulum stress is a central feature of obesity, insulin resistance, and type 2 diabetes. A polymorphism of the XBP1 gene (-116C/G), a transcription factor that modulates the endoplasmic reticulum stress response, causes an impairment of its positive feedback system. The authors examined a role of the polymorphism in the development of obesity. The polymorphism was investigated in clinically obese children and compared with controls. Significant difference of genotype distribution was observed, which suggested that the -116C/G genotype may be a risk factor for at least pediatric obesity.
Hampton RYER stress response: getting the UPR hand on misfolded proteins. Curr Biol. 2000;10:R518-R521.
2.
Harding HP, Calfon M., Urano F., Novoa I., Ron D.Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol. 2002;18:575-599.
3.
Mori K.Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell. 2000;101:451-454.
4.
Oyadomari, S. & Mori, M.Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004;11:381-389.
5.
Ozcan U., Cao Q., Yilmaz E., et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457-461.
6.
Wang XZ, Harding HP, Zhang Y., Jolicoeur EM, Kuroda M., Ron D.Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 1998;17:5708-5717.
7.
Nikawa J., Yamashita S.IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae. Mol Microbiol. 1992;6:1441-1446.
8.
Mori K., Ma W., Gething MJ, Sambrook J.A transmembrane protein with a CDC2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell. 1993;74:743-756.
9.
Tirasophon W. , Welihinda AA, Kaufman RJA stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 1998 ;12:1812-1824.
10.
Bork P., Sander C.A hybrid protein kinase-RNase in an interferon-induced pathway? FEBS Lett. 1993;334:149-152.
11.
Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K.XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107:881-891.
12.
Calfon M., Zeng H., Urano F., et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002 ;415:92-96.
13.
Liou HC, Boothby MR, Finn PW, et al. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 1990 ;247:1581-1584.
14.
Lee AH, Iwakoshi NN, Glimcher LHXBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003;23:7448-7459.
15.
Hirosumi J. , Tuncman G., Chang L., et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333-336.
16.
Rui L., Aguirre V., Kim JK, et al. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest . 2001;107:181-189.
17.
Kakiuchi C., Iwamoto K., Ishiwata M., et al. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat Genet. 2003;35:171-175.
18.
Kato C., Kakiuchi C., Umekage T., et al. XBP1 gene polymorphism (-116C/G) and personality. Am J Med Genet B Neuropsychiatr Genet. 2005;136:103-105.
19.
Watanabe Y., Fukui N., Muratake T., et al. Association study of a functional promoter polymorphism of the X-box binding protein 1 gene in Japanese patients with schizophrenia. Psychiatry Clin Neurosci. 2006;60:633-635.
20.
Jonsson EG, Cichon S., Schumacher J., et al. Association study of a functional promoter polymorphism in the XBP1 gene and schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006;141:71-75.
21.
Wu J., Kaufman RJFrom acute ER stress to physiological roles of the unfolded protein response . Cell Death Differ. 2006;13:374-384.
22.
Harding HP, Ron D.Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes. 2002; 51(suppl 3):S455-S461.
23.
Vasa-Nicotera M.The new kid on the block: the unfolded protein response in the pathogenesis of atherosclerosis. Cell Death Differ. 2004;11(suppl 1):S10-S11.
24.
Marchetti P. , Bugliani M., Lupi R., et al. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia. 2007;50:2486-2494.
25.
Ozcan U., Yilmaz E., Ozcan L., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313: 1137-1140.
26.
Berberoglu M., Evliyaoglu O., Adiyaman P., et al. Plasminogen activator inhibitor-1 (PAI-1) gene polymorphism (-675 4G/5G) associated with obesity and vascular risk in children. J Pediatr Endocrinol Metab. 2006;19:741-748.
