Association Between First Episode Schizophrenia, Metabolic Syndrome and Insulin Resistance-Related Proteins in Female Balb/C Mice
Abstract
Background: Metabolic syndrome is a group of different disorders mainly includes, insulin resistance, obesity, cerebrovascular disorders, dyslipidemia, which leads to increase mortality. Patients suffering from related psychotic disorders such as schizophrenia are at the higher risk of developing metabolic syndrome. The aim of this study was to evaluate the association between the first episode of schizophrenia, metabolic syndrome and insulin resistance-related proteins in blood and adipose tissue of mice.Materials and Methods: Twelve, female Balb/c mice were randomly divided into two groups; one group was injected intraperitoneal MK-801 (0.6mg/kg/d) to induce schizophrenia, and other group received the 0.9% normal saline for two weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance (OGT), and Homeostatic model assessment (HOMA), were observed. Blood and adipose tissue were collected and Western blotting was done to evaluate the insulin resistance related proteins (GGPPS, FAT, PTP-1B, GRK2, ATGL, FGF21, and PGC-1α) by using GAPDH as an internal standard. Results: There was a significant increase in mean body weight in schizophrenic group (21.76 vs 22.81, P=004). On day 14, the FBG, insulin concentrations and Homeostatic model assessment and insulin resistance (HOME-IR) were high in schizhphrenic group vs control group, e.g. 5.3±0.6 vs 3.47±0.2 (P=0.0001), 28.9±2.2 vs 23.3±0.6 (P<0.005) and 9.2±1.3 vs 3.9±0.2 (P=0.0001) . Impaired glucose tolerance deranged from 4.8mmol/L to 6.4mmol/L. Western blotting showed a marked increase in the expression of GGPPS, FAT, ATGL, and FGF21 proteins in monocytes and PTP-1B, GRK2, and PGC-1α ratios in adipose tissues.Conclusion: There was a positive relation between schizophrenia and metabolic syndrome e.g. insulin resistance and obesity. Certain proteins in adipocytes and blood were responsible for causing insulin resistance. [GMJ.2018;7:e692]References
Malhotra N, Grover S, Chakrabarti S, Kulhara P. Metabolic syndrome in schizophrenia. Indian J Psychol Med. 2013;35(3):227. https://doi.org/10.4103/0253-7176.119471. PMid:24249923 PMCid:PMC3821198
Gill H, Mugo M, Whaley-Connell A, Stump C, Sowers JR. Am J Med Sci. 2005;330(6):290-4.
https://doi.org/10.1097/00000441-200512000-00006
PMid:16355013
Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell metab. 2005;1(6):361-70.
https://doi.org/10.1016/j.cmet.2005.05.004
PMid:16054085
Tao W, Wu J, Xie BX, Zhao YY, Shen N, Jiang S, et al. Lipid-induced Muscle Insulin Resistance Is Mediated by GGPPS via Modulation of the RhoA/Rho Kinase Signaling Pathway. J Biol Chem. 2015;290(33):20086-97.
https://doi.org/10.1074/jbc.M115.657742
PMid:26112408 PMCid:PMC4536415
Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006;312(5774):734-7.
https://doi.org/10.1126/science.1123965
PMid:16675698
Koonen DP, Glatz JF, Bonen A, Luiken JJ. Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta. 2005;1736(3):163-80. https://doi.org/10.1016/j.bbalip.2005.08.018
PMid:16198626
Luo DQ, Liu ZQ, Liu T, Chen C, Li MY, Wang ZY, et al. Data in support of fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice. Data in brief. 2015;4:159.
Garcia-Guerra L, Nieto-Vazquez I, Vila-Bedmar R, Jurado-Pueyo M, Zalba G, Díez J, et al. G protein–coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity. Diabetes. 2010;59(10):2407-17.
https://doi.org/10.2337/db10-0771
PMid:20627936 PMCid:PMC3279564
Ramos A, Berton O, Mormède P, Chaouloff F. A multiple-test study of anxiety-related behaviours in six inbred rat strains. Behav Brain Res. 1997;85(1):57-69.
https://doi.org/10.1016/S0166-4328(96)00164-7
Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, et al. Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes care. 1999;22(5):818-22. https://doi.org/10.2337/diacare.22.5.818
PMid:10332688
Papanastasiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review. Ther Adv Psychopharmacol. 2013;3(1):33-51.
https://doi.org/10.1177/2045125312464385
PMid:23983991 PMCid:PMC3736963
Bartoli F, Crocamo C, Caslini M, Clerici M, Carrà G. Schizoaffective disorder and metabolic syndrome: A meta-analytic comparison with schizophrenia and other non-affective psychoses. J Psychiatr Res. 2015;66:127-34.
https://doi.org/10.1016/j.jpsychires.2015.04.028
PMid:26004300
Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003;163(4):427-36.
https://doi.org/10.1001/archinte.163.4.427
PMid:12588201 PMCid:PMC3146257
Vila-Bedmar R, Cruces-Sande M, Lucas E, Willemen HL, Heijnen CJ, Kavelaars A, et al. Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2. Sci Signal. 2015;8(386):ra73.
https://doi.org/10.1126/scisignal.aaa4374
PMid:26198359 PMCid:PMC4586018
Schoiswohl G, Stefanovic-Racic M, Menke MN, Wills RC, Surlow BA, Basantani MK, et al. Impact of reduced ATGL-mediated adipocyte lipolysis on obesity-associated insulin resistance and inflammation in male mice. Endocrinology. 2015;156(10):3610-24.
https://doi.org/10.1210/en.2015-1322
PMid:26196542 PMCid:PMC4588821
Bernardo B, Lu M, Bandyopadhyay G, Li P, Zhou Y, Huang J, et al. FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance. Scientific reports. 2015;5. https://doi.org/10.1038/srep11382
Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders-a systematic review and meta-analysis. Schizophr Bull. 2011;39(2):306-18. https://doi.org/10.1093/schbul/sbr148
PMid:22207632 PMCid:PMC3576174
Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, Rosenbaum S, Correll CU. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015:1;14(3):339-47.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
