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Обозрение психиатрии и медицинской психологии имени В.М.Бехтерева

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Изучение механизмов метаболических нарушений, индуцированных антипсихотическими препаратами: возможности использования клеточных моделей

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Аннотация

Терапия антипсихотическими препаратами и первой, и второй генерации сопровождается метаболическими побочными эффектами. Работами последних лет выявлены некоторые механизмы реализации антипсихотик-индуцированных метаболических нарушений - центральные (индукция резистентности к гормону насыщения лептину, изменение уровня адипонектина, угнетающего глюко-неогенез и повышающего чувствительность клеток к инсулину) и периферические (активация системы белков SREBP, осуществляющих транскрипцию генов биосинтеза холестерина и жирных кислот, наряду с ингибированием поздних этапов синтеза холестерина; а также изменения внутриклеточного транспорта холестерина). Перспективным является изучение взаимосвязи возникновения метаболических нарушений при лечении АП с изменениями продукции цитокинов и других факторов воспаления. Часть таких исследований, также как и исследований периферических механизмов побочных эффектов АП могут быть эффективно выполнены in vitro на моделях культивируемых клеток, в первую очередь, печеночного происхождения.

Об авторах

Р. Ф. Насырова
Санкт-Петербургский научно-исследовательский психоневрологический институт им. В.М. Бехтерева
Россия


В. В. Тепляшина
Санкт-Петербургский научно-исследовательский психоневрологический институт им. В.М. Бехтерева
Россия


Д. В. Иващенко
Санкт-Петербургский научно-исследовательский психоневрологический институт им. В.М. Бехтерева
Россия


С. А. Снопов
ФБГУН «Институт цитологии» РАН
Россия


Список литературы

1. Алфимов П.В., Рывкин П.В., Ладыженский М.Я., Мосолов С.Н. Метаболический синдром у больных шизофренией (обзор литературы) // Современная терапия психических расстройств - 2014. - № 3. - С. 8-14

2. Незнанов Н.Г., Мартынихин И.А., Танянский Д.А., Ротарь О.П., Солнцев В.Н., Соколян Н.А., Конради А.О., Денисенко А.Д. Шизофрения - фактор, увеличивающий риск развития метаболического синдрома. Результаты исследования с использованием метода подбора пар // Медицинский академический журнал. - 2013. - № 3(13). - С. 90-96

3. Adachi H., Yanai H., Hirowatari Y. The Underlying Mechanisms for Olanzapine-induced Hypertriglyceridemia // J Clin Med Res. - 2012. - V. 4 (3) - P.206-8

4. Andersson N., Strandberg L., Nilsson S. et al. A variant near the interleukin-6 gene is associated with fat mass in Caucasian men // Int J Obes (Lond). - 2010. - V. 34. - P. 1011-1019

5. Andersson N., Strandberg L., Nilsson S. et al. Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men // Int J Obes (Lond). - 2009. - V. 33. - P. 525-533

6. Balt S.L., Galloway G.P., Baggott M.J., Schwartz Z., Mendelson J. Mechanisms and genetics of antipsychotic-associated weight gain // Clin Pharmacol Ther. - 2011. - V. 90(1). - P. 179-83

7. Bartoli F., Crocamo C., Clerici M., Carrà G. Second-generation antipsychotics and adiponectin levels in schizophrenia: A comparative meta-analysis // Eur Neuropsychopharmacol. - 2015. - V. 25 (10). - P. 1767-74

8. Basta-Kaim A., Szczçsny E., Leskiewicz M. et al. Maternal immune activation leads to age-related behavioral and immunological changes in male rat offspring - the effect of antipsychotic drugs // Pharmacological reports. - 2012. - V. 64 (6). - P. 1400-10

9. Bastard J.P., Maachi M., Lagathu C. et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance // Eur Cytokine Netw. - 2006. V.17. - P. 4-12

10. Berthier M.T., Paradis A.M., Tchernof A. et al. The interleukin 6-174G/C polymorphism is associated with indices of obesity in men // J Hum Genet. - 2003. - V.48. - P. 14-19

11. Bochud M., Marquant F., Marques-Vidal P.M., et al. Association between C-reactive protein and adiposity in women // Journal of Clinical Endocrinology and Metabolism. - 2009. - V. 94 (10). - P. 3969-3977

12. Canfrän-Duque A., Casado M.E., Pastor O. et al. Atypical antipsychotics alter cholester ol and fatty acid metabolism in vitro //J Lipid Res. - 2013. - V.54 (2). - P. 310-24

13. Chen M.L., Wu S., Tsai T.C., Wang L.K., Tsai F.M. Regulation of macrophage immune responses by antipsychotic drugs // Immunopharmacol Im-munotoxicol. - 2013. - V. 35 (5). - P. 573-80

14. Church C., Lee S., Bagg E.A., McTaggart J.S. et al. A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene // PLoS Genet. - 2009. - V. 5(8)

15. Contreras-Shannon V., Heart D.L., Paredes R.M., Navaira E., Catano G., Maffi S.K., Walss-Bass C. Clozapine-induced mitochondria alterations and inflammation in brain and insulin-responsive cells // PLoS One. - 2013. - V. 8(3). - e59012.

16. Davey K.J., O’Mahony S.M., Schellekens H., O’Sullivan O., Bienenstock J., Cotter P.D., Dinan T.G., Cryan J.F. Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters // Psychopharmacology (Berl). - 2012. - V. 221(1). - P. 155-69.

17. De Alvaro C., Teruel T., Hernandez R., Lorenzo M. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner // J Biol Chem. - 2004. - V. 279(17). - P. 17070-8.

18. Dina C., Meyre D., Gallina S., Durand E. et al. Variation in FTO contributes to childhood obesity and severe adult obesity // Nat Genet. - 2007. - V. 39 (6). - P. 724-6

19. Donato M.T., Jover R., Gomez-Lechon M.J. Hepatic cell lines for drug hepatotoxicity testing: limitations and strategies to upgrade their metabolic competence by gene engineering // Curr Drug Metab. - 2013. - V. 14. - P. 946-968.

20. Drzyzga L., Obuchowicz E., Marcinowska A., Herman Z.S. Cytokines in schizophrenia and the effects of antipsychotic drugs // Brain Behav Immun. - 2006. - V. 20. - P. 532-545.

21. Fernandes B. S.et al. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications // Mol. Psychiatry. - 2015 - V. 87

22. Fern0 J., Skrede S., Vik-Mo A.O., Hâvik B., Steen V.M. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs // BMC Neurosci. - 2006. - V. 7. - P. 69.

23. Fern0 J., Vik-Mo A.O., Jassim G., Hâvik B., Berge K. et al. Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver // Psychopharmacology (Berl). - 2009. - V. 203 (1). - P. 73-84.

24. Fonseka T.M.-Müller D.J.-Kennedy S.H. Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications // Mol Neuropsychiatry. - 2016. - V. 2. - P. 1-14

25. Frayling T.M., Timpson N.J., Weedon M.N., Zeg-gini E. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity // Science. - 2007. - V. 316 (5826). - P. 889-94

26. Girault E.M., Alkemade A., Foppen E. et al. Acute-peripheral but not central administration of olanzapine induces hyperglycemiaassociated with hepatic and extra-hepatic insulin resistance // PLoS One. - 2012. - V. 7 (8). - e43244.

27. Gômez-Lechôn M.J., Tolosa L., Donato M.T. Cell-based models to predict human hepatotoxicity of drugs // Rev. Toxicol. - 2014. V. 31. - P. 149-156

28. Gômez-Lechôn, M.J., Donato, T., Ponsoda, X., Fab-ra, R., Trullenque, R., Castell, J.V. Isolation, culture and use of human hepatocytes in drug research in: J.V. Castell, M.J. Gômez-Lechôn (Eds.) In vitro methods in pharmaceutical research // Academic Press, San Diego, CA. - 1997. - P. 129-153.

29. Gonçalves P., Araüjo J.R., Martel F. Antipsychotics-induced metabolic alterations: focus on adipose tissue and molecular mechanisms // Eur Neuropsychopharmacol. - 2015. - V. 25 (1). - P. 1-16.

30. Goyenechea E., Parra D., Martinez J.A. Impact of interleukin 6 -174G>C polymorphism on obesity-related metabolic disorders in people with excess in body weight // Metabolism. - 2007. - V. 56. - P. 1643-1648.

31. Jassim G., Ferrn J., Theisen F.M., Haberhausen M. et al. Association study of energy homeostasis genes and antipsychotic-induced weight gain in patients with schizophrenia // Pharmacopsychiatry. - 2011. - V. 44 (1) - P. 15-20.

32. Kadowaki T., Yamauchi T., Kubota N., Hara K., Ueki K., Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome // J Clin Invest. - 2006. V. 116 (7). - P. 1784-92.

33. Kanebratt K.P., Andersson T.B. Evaluation of HepaRG cellsas an in vitro model for human drug metabolism studies // Drug Metab Dispos. - 2008. - V. 36. - P. 1444-1452.

34. Kopp H.P., Kopp C.W., Festa A. et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients // Arterioscler Thromb Vasc Biol. - 2003. - V. 23. - P. 1042-1047.

35. Kristiana I., Sharpe L.J., Catts VS., Lutze-Mann L.H., Brown A.J. Antipsychotic drugs upregulate lipogenic gene expression by disrupting intracellular trafficking of lipoprotein-derived cholesterol // Pharmacogenomics J. - 2010 - V. 10(5). - P. 396-407.

36. Kroeze W.K., Hufeisen S.J. et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs // Neuropsychopharmacology. - 2003. - V. 28(3). - P. 519

37. Leonard B.E., Schwarz M., Myint A.M. The metabolic syndrome in schizophrenia: is inflammation a contributing cause? // J Psychopharmacol. - 2012. - V. 26. - P. 33-41.

38. Lett T.A., Wallace T.J., Chowdhury N.I., Tiwari A.K., Kennedy J.L., Müller D.J. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications // Mol Psychiatry. - 2012 - V. 17. - P. 242-266.

39. Madan A., Graham R., Carroll K. et al. Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes // Drug Metab Dispos. - 2003. - V. 31. - P. 421

40. Maurel P. The use of adult human hepatocytes in primary culture and other in vitro systems to investigate drug metabolism in man // Advanced Drug Delivery Reviews. - 1996. - V. 22. - P. 105-132.

41. Meyer U., Schwarz M.J., Muller N. Inflammatory processes in schizophrenia: a promising neuroim-munological target for the treatment of negative/ cognitive symptoms and beyond // Pharmacol Ther. - 2011. - V.32. - P. 96-110.

42. Miller A.H., Raison C.L. The role of inflammation in depression: from evolutionary imperative to modern treatment target // Nat Rev Immunol. - 2016. - V. 16 (1). - P. 22-34.

43. Monteiro R., Azevedo I. Chronic inflammation in obesity and the metabolic syndrome // Mediators Inflamm. - 2010. - pii: 289645.

44. Müller D.J., Zai C.C., Sicard M., Remington E. et al. Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain // Pharmacogenomics J. - 2012. - V. 12(2). - P. 156-64.

45. Müller N., Myint A.M., Schwarz M.J. Inflammation in schizophrenia // Adv Protein Chem Struct Biol. - 2012. - V. 88. - P. 49-68.

46. Nijhuis J., Rensen S.S., Slaats Y., et al. Neutrophil activation in morbid obesity, chronic activation of acute inflammation // Obesity. - 2009. - V. 17 (11). - P. 2014-2018.

47. O’Brien P.J., Irwin W., Diaz D. et al. High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening // Arch Toxicol. - 2006. V. 80. - P. 580-604.

48. Pavan C., Vindigni V., Michelotto L., Rimessi A. et al. Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-ß // Pharmacogenomics J. - 2010. - V. 10(5). - PA0817

49. Perez-Iglesias R., Vazquez-Barquero J.L., Amado J.A. et al. Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment // J Clin Psychopharmacol. - 2008. - V. 28 (3). - P. 289-95.

50. Raison C. L.et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers // JAMA Psychiatry. - 2013.--V. 70. - P. 31-41

51. Risselada A.J., Mulder H., Heerdink E.R., Egberts T.C. Pharmacogenetic testing to predict antipsychotic-induced weight gain: a systematic review // Pharmacogenomics. - 2011. - V. 12(8). - P. 1213 -27.

52. Ruan H., Miles P.D., Ladd C.M. et al. Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factoralpha: implications for insulin resistance // Diabetes. - 2002. - V.51 (11). - P. 3176-88.

53. Sânchez-Wandelmer J., Hernândez-Pinto A.M., Cano S. et al. Effects of the antipsychotic drug haloperidol on the somastostatinergic system in SH-SY5Y neuroblastoma cells // J Neurochem. - 2009. - V. 110(2). - P. 631-40.

54. Sârvâri A.K., Veréb Z., Uray I.P., Fésüs L., Balajthy Z. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro // Biochem Biophys Res Commun. - 2014. - V.450. - P. 1383-1389.

55. Sassa S., Sugita O., Galbraith R.A., Kappas A. Drug metabolism by the human hepatoma cell, HepG2 // Biochem Biophys Res Commun. - 1987. - V. 143. - P. 52-57

56. Schoonen W.G., Stevenson J.C., Westerink W.M., Horbach G.J. Cytotoxic effects of 109 reference compounds on rat H4IIE and human HepG2 hepatocytes. III: Mechanistic assays on oxygen consumption with MitoXpress and NAD (P)H production with Alamar Blue // Toxicol In Vitro. - 2012. - V. 26. - P. 511-525.

57. Sertié A.L., Suzuki A.M., Sertié R.A. et al. Effects of antipsychotics with different weight gain liabilities on human in vitro models of adipose tissue differentiation and metabolism // Prog Neuropsychopharmacol Biol Psychiatry. - 2011. - V. 35 (8). - P. 1884-90

58. Sicard M.N., Zai C.C., Tiwari A.K., Souza R.P. et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis // Pharmacogenomics. - 2010. - V.11(11). - P. 1561-71.

59. Strandberg L., Mellstrom D., Ljunggren O. et al. IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden // Obesity (Silver Spring). - 2008. - V. 16. - P. 710-713.

60. Tourjman V., Kouassi E., Koue M.E. et al. Antipsychotics’ effects on blood levels of cytokines in schizophrenia: a meta-analysis // Schizophrenia Research. - 2013. - V. 151(1-3). - P. 43-47

61. Tsai S.J. Is mania caused by overactivity of central brain-derived neurotrophic factor? // Med Hypotheses. - 2004. -V. 62(1). - P. 19-22.

62. Uçok A., Gaebel W. Side effects of atypical antipsychotics: a brief overview // World Psychiatry. - 2008. - V. 7(1). - P. 58-62.

63. Um J.Y., Rim H.K., Kim S.J., Kim H.L., Hong S.H: Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice // PLoS One. - 2011. - V. 6. - e29524.

64. Vehof J., Risselada A.J., Hadithy A.F., Burger H. et al. Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication //Psychopharmacology (Berl). - 2011. - P. 216 (2). - V. 257-65.

65. Wang Y.C., Bai Y.M., Chen J.Y., Lin C.C., Lai I.C., Liou Y.J. Genetic association between TNF-alpha -308 G>A polymorphism and longitudinal weight change during clozapine treatment // Hum Psychopharmacol. - 2010. - V. 25. - P. 303-309.

66. Westerink W.M.A., Schoonen W.G. Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells // Toxicol In Vitro. - 2007. -V. 21. - P. 1592-1602

67. Xu Y., Jones J.E., Kohno D. et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis // Neuron. - 2008. - V. 60(4). - P. 582-589.

68. Yang L.H., Chen T.M., Yu S.T., Chen Y.H. Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells // Pharmacol Res. - 2007. - V.56(3). - P. 202-8.

69. Zhang J.P., Malhotra A.K. Genetics of schizophrenia: What do we know? // Curr Psychi-atr. - 2013. - V.12 (3). - P.24-33.

70. Zhang X.Y., Zhou D.F., Wu G.Y. et al. BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia // Neuropsychopharmacology. - 2008. - V.33 (9). - P. 2200-5.


Для цитирования:


Насырова Р.Ф., Тепляшина В.В., Иващенко Д.В., Снопов С.А. Изучение механизмов метаболических нарушений, индуцированных антипсихотическими препаратами: возможности использования клеточных моделей. Обозрение психиатрии и медицинской психологии имени В.М.Бехтерева. 2016;(4):52-60.

For citation:


Nasyrova R.F., Teplyashina V.V., Ivashchenko D.V., Snopov S.A. Study of mechanisms of antipsychotic-induced metabolic disturbances: potential for application of cellular models. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. 2016;(4):52-60. (In Russ.)

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