Dysregulated glutathione metabolism links to impaired insulin action in adipocytes - PubMed (original) (raw)
. 2009 Jun;296(6):E1326-34.
doi: 10.1152/ajpendo.90921.2008. Epub 2009 Apr 14.
Affiliations
- PMID: 19366877
- DOI: 10.1152/ajpendo.90921.2008
Free article
Dysregulated glutathione metabolism links to impaired insulin action in adipocytes
Hironori Kobayashi et al. Am J Physiol Endocrinol Metab. 2009 Jun.
Free article
Abstract
Oxidative stress plays an important role in obesity-related metabolic diseases. Glutathione peroxidase (GPX) is an antioxidant enzyme downregulated in adipose tissue of obese mice. However, the role of GPX in adipocytes remains elusive. The objective of this study was to clarify the pathophysiological changes in GPX activity and glutathione metabolism and their roles in the pathogenesis of insulin resistance in adipocytes. To achieve this goal, we measured cellular GPX activity, glutathione (GSH) contents, GSH/GSSG ratio, and mRNA expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for de novo GSH synthesis, in adipose tissue of control and ob/ob mice and in 3T3-L1 adipocytes treated with insulin, H(2)O(2), free fatty acid (FFA), or TNFalpha. Furthermore, we investigated the effects of GPX inhibition with a specific GPX inhibitor or RNA interference against GPX, H(2)O(2), and reduced GSH on insulin signaling in 3T3-L1 adipocytes. ob/ob Mice showed not only a decrease in cellular activity of GPXs (GPX1, -4, and -7) but also an increase in gamma-GCS expression, resulting in increased GSH contents in adipose tissue. These alterations in glutathione metabolism were also observed during differentiation of 3T3-L1 cells and their exposure to insulin, FFA, or H(2)O(2). Inhibition of GPX activity, addition of GSH, and H(2)O(2) resulted in impaired insulin signaling in 3T3-L1 adipocytes. These results suggest that decreased GPX activity and increased gamma-GCS expression lead to overaccumulation of GSH, which might be involved in the pathogenesis of insulin resistance in obesity.
Similar articles
- Effects of fatty acid regulation on visfatin gene expression in adipocytes.
Wen Y, Wang HW, Wu J, Lu HL, Hu XF, Cianflone K. Wen Y, et al. Chin Med J (Engl). 2006 Oct 20;119(20):1701-8. Chin Med J (Engl). 2006. PMID: 17097017 - Regulation of gamma-glutamate-cysteine ligase expression by oxidative stress in the mouse preimplantation embryo.
Stover SK, Gushansky GA, Salmen JJ, Gardiner CS. Stover SK, et al. Toxicol Appl Pharmacol. 2000 Oct 15;168(2):153-9. doi: 10.1006/taap.2000.9030. Toxicol Appl Pharmacol. 2000. PMID: 11032771 - The role of adipocyte insulin resistance in the pathogenesis of obesity-related elevations in endocannabinoids.
D'Eon TM, Pierce KA, Roix JJ, Tyler A, Chen H, Teixeira SR. D'Eon TM, et al. Diabetes. 2008 May;57(5):1262-8. doi: 10.2337/db07-1186. Epub 2008 Feb 14. Diabetes. 2008. PMID: 18276766 - Glutathione metabolism during aging and in Alzheimer disease.
Liu H, Wang H, Shenvi S, Hagen TM, Liu RM. Liu H, et al. Ann N Y Acad Sci. 2004 Jun;1019:346-9. doi: 10.1196/annals.1297.059. Ann N Y Acad Sci. 2004. PMID: 15247041 Review. - Genetically altered mice to evaluate glutathione homeostasis in health and disease.
Dalton TP, Chen Y, Schneider SN, Nebert DW, Shertzer HG. Dalton TP, et al. Free Radic Biol Med. 2004 Nov 15;37(10):1511-26. doi: 10.1016/j.freeradbiomed.2004.06.040. Free Radic Biol Med. 2004. PMID: 15477003 Review.
Cited by
- Exercise-Induced Adipose Tissue Thermogenesis and Browning: How to Explain the Conflicting Findings?
Zhu Y, Qi Z, Ding S. Zhu Y, et al. Int J Mol Sci. 2022 Oct 28;23(21):13142. doi: 10.3390/ijms232113142. Int J Mol Sci. 2022. PMID: 36361929 Free PMC article. Review. - Serum γ-glutamyltransferase level and incidence risk of metabolic syndrome in community dwelling adults: longitudinal findings over 12 years.
Kwak J, Seo IH, Lee YJ. Kwak J, et al. Diabetol Metab Syndr. 2023 Feb 23;15(1):29. doi: 10.1186/s13098-023-01000-5. Diabetol Metab Syndr. 2023. PMID: 36823659 Free PMC article. - Selenium-binding protein 1 (SELENBP1) is a marker of mature adipocytes.
Steinbrenner H, Micoogullari M, Hoang NA, Bergheim I, Klotz LO, Sies H. Steinbrenner H, et al. Redox Biol. 2019 Jan;20:489-495. doi: 10.1016/j.redox.2018.11.004. Epub 2018 Nov 10. Redox Biol. 2019. PMID: 30469030 Free PMC article. - Oxidative Stress-Related Susceptibility to Aneurysm in Marfan's Syndrome.
Rysz J, Gluba-Brzózka A, Rokicki R, Franczyk B. Rysz J, et al. Biomedicines. 2021 Sep 6;9(9):1171. doi: 10.3390/biomedicines9091171. Biomedicines. 2021. PMID: 34572356 Free PMC article. Review. - Links between ectopic fat and vascular disease in humans.
Lim S, Meigs JB. Lim S, et al. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1820-6. doi: 10.1161/ATVBAHA.114.303035. Epub 2014 Jul 17. Arterioscler Thromb Vasc Biol. 2014. PMID: 25035342 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous