Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects?
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| Title: | Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? |
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| Authors: | Le Hellard, S., Theisen, F. M., Haberhausen, M., Raeder, M. B., Fernø, J., Gebhardt, S., Hinney, A., Remschmidt, H., Krieg, J. C., Mehler-Wex, C., Nöthen, M. M., Hebebrand, J., Steen, V. M. |
| Source: | Molecular Psychiatry. Mar2009, Vol. 14 Issue 3, p308-317. 10p. 2 Diagrams, 2 Charts. |
| Subjects: | Side effects of antipsychotic drugs, Weight gain, Psychoses, Schizophrenia, Genetic polymorphisms, Sterols |
| Abstract: | Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003–0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.Molecular Psychiatry (2009) 14, 308–317; doi:10.1038/sj.mp.4002133; published online 15 January 2008 [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 36555331 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Le+Hellard%2C+S%2E%22">Le Hellard, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Theisen%2C+F%2E+M%2E%22">Theisen, F. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Haberhausen%2C+M%2E%22">Haberhausen, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Raeder%2C+M%2E+B%2E%22">Raeder, M. B.</searchLink><br /><searchLink fieldCode="AR" term="%22Fernø%2C+J%2E%22">Fernø, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Gebhardt%2C+S%2E%22">Gebhardt, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Hinney%2C+A%2E%22">Hinney, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Remschmidt%2C+H%2E%22">Remschmidt, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Krieg%2C+J%2E+C%2E%22">Krieg, J. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Mehler-Wex%2C+C%2E%22">Mehler-Wex, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Nöthen%2C+M%2E+M%2E%22">Nöthen, M. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Hebebrand%2C+J%2E%22">Hebebrand, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Steen%2C+V%2E+M%2E%22">Steen, V. M.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Mar2009, Vol. 14 Issue 3, p308-317. 10p. 2 Diagrams, 2 Charts. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Side+effects+of+antipsychotic+drugs%22">Side effects of antipsychotic drugs</searchLink><br /><searchLink fieldCode="DE" term="%22Weight+gain%22">Weight gain</searchLink><br /><searchLink fieldCode="DE" term="%22Psychoses%22">Psychoses</searchLink><br /><searchLink fieldCode="DE" term="%22Schizophrenia%22">Schizophrenia</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Sterols%22">Sterols</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003–0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.Molecular Psychiatry (2009) 14, 308–317; doi:10.1038/sj.mp.4002133; published online 15 January 2008 [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/sj.mp.4002133 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 308 Subjects: – SubjectFull: Side effects of antipsychotic drugs Type: general – SubjectFull: Weight gain Type: general – SubjectFull: Psychoses Type: general – SubjectFull: Schizophrenia Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Sterols Type: general Titles: – TitleFull: Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Le Hellard, S. – PersonEntity: Name: NameFull: Theisen, F. M. – PersonEntity: Name: NameFull: Haberhausen, M. – PersonEntity: Name: NameFull: Raeder, M. B. – PersonEntity: Name: NameFull: Fernø, J. – PersonEntity: Name: NameFull: Gebhardt, S. – PersonEntity: Name: NameFull: Hinney, A. – PersonEntity: Name: NameFull: Remschmidt, H. – PersonEntity: Name: NameFull: Krieg, J. C. – PersonEntity: Name: NameFull: Mehler-Wex, C. – PersonEntity: Name: NameFull: Nöthen, M. M. – PersonEntity: Name: NameFull: Hebebrand, J. – PersonEntity: Name: NameFull: Steen, V. M. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2009 Type: published Y: 2009 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 14 – Type: issue Value: 3 Titles: – TitleFull: Molecular Psychiatry Type: main |
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