Identification and expression analysis of leptin-regulated immediate early response and late target genes

W Waelput, A Verhee, D Broekaert, S Eyckerman, J Vandekerckhove, J H Beattie, J Tavernier

    Research output: Contribution to journalArticle

    51 Citations (Scopus)

    Abstract

    Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation of the leptin receptor. On the basis of kinetic studies, two distinct gene sets could be discerned: signal transducer and activator of transciption-3 (STAT-3), suppressor of cytokine signalling-3 (SOCS-3), MT-II (metallothionein-II), the serine/threonine kinase fibroblast-growth-factor-inducible kinase (Fnk) and modulator recognition factor (MRF-1), which are immediate early response genes, and pancreatitis-associated protein I (PAP I), squalene epoxidase, uridine diphosphate glucuronosyltransferase and annexin VIII, which are late induced target genes. At late time points a strong co-stimulation with beta-nerve growth factor or with the adenylate cyclase activator forskolin was observed. To assess the validity of the PC12-cell model system, we examined the effect of leptin administration on the gene transcription of STAT-3, MT-II, Fnk and PAP I in vivo. Leptin treatment of leptin-deficient ob/ob mice increased the STAT-3, SOCS-3, MT-II and Fnk mRNA, and MT-I protein levels in liver, whereas, in jejunum, expression of PAP I mRNA was down-regulated. Furthermore, administration of leptin to starved wild-type mice enhanced the expression of MT-II and Fnk mRNA in liver, but decreased MT-II and PAP I mRNA expression in jejunum. These findings may help to explain the obese phenotype observed in some colonies of MT-I- and MT-II-null mice and/or the observation that leptin protects against tumour-necrosis-factor toxicity in vivo.

    Original languageEnglish
    Pages (from-to)55-61
    Number of pages7
    JournalBiochemical Journal
    Volume348
    Publication statusPublished - 15 May 2000

    Keywords

    • forskolin
    • gene induction
    • metallothionein
    • PC12 cells
    • representational difference analysis
    • REPRESENTATIONAL DIFFERENCE ANALYSIS
    • MESSENGER-RNA EXPRESSION
    • METALLOTHIONEIN-II GENES
    • IN-SITU HYBRIDIZATION
    • OBESE GENE
    • BODY-WEIGHT
    • PERIPHERAL-TISSUES
    • NEUROPEPTIDE-Y
    • DIABETIC MICE
    • DB/DB MICE

    Cite this

    Waelput, W., Verhee, A., Broekaert, D., Eyckerman, S., Vandekerckhove, J., Beattie, J. H., & Tavernier, J. (2000). Identification and expression analysis of leptin-regulated immediate early response and late target genes. Biochemical Journal, 348, 55-61.

    Identification and expression analysis of leptin-regulated immediate early response and late target genes. / Waelput, W ; Verhee, A ; Broekaert, D ; Eyckerman, S ; Vandekerckhove, J ; Beattie, J H ; Tavernier, J .

    In: Biochemical Journal, Vol. 348, 15.05.2000, p. 55-61.

    Research output: Contribution to journalArticle

    Waelput, W, Verhee, A, Broekaert, D, Eyckerman, S, Vandekerckhove, J, Beattie, JH & Tavernier, J 2000, 'Identification and expression analysis of leptin-regulated immediate early response and late target genes', Biochemical Journal, vol. 348, pp. 55-61.
    Waelput W, Verhee A, Broekaert D, Eyckerman S, Vandekerckhove J, Beattie JH et al. Identification and expression analysis of leptin-regulated immediate early response and late target genes. Biochemical Journal. 2000 May 15;348:55-61.
    Waelput, W ; Verhee, A ; Broekaert, D ; Eyckerman, S ; Vandekerckhove, J ; Beattie, J H ; Tavernier, J . / Identification and expression analysis of leptin-regulated immediate early response and late target genes. In: Biochemical Journal. 2000 ; Vol. 348. pp. 55-61.
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    T1 - Identification and expression analysis of leptin-regulated immediate early response and late target genes

    AU - Waelput, W

    AU - Verhee, A

    AU - Broekaert, D

    AU - Eyckerman, S

    AU - Vandekerckhove, J

    AU - Beattie, J H

    AU - Tavernier, J

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    N2 - Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation of the leptin receptor. On the basis of kinetic studies, two distinct gene sets could be discerned: signal transducer and activator of transciption-3 (STAT-3), suppressor of cytokine signalling-3 (SOCS-3), MT-II (metallothionein-II), the serine/threonine kinase fibroblast-growth-factor-inducible kinase (Fnk) and modulator recognition factor (MRF-1), which are immediate early response genes, and pancreatitis-associated protein I (PAP I), squalene epoxidase, uridine diphosphate glucuronosyltransferase and annexin VIII, which are late induced target genes. At late time points a strong co-stimulation with beta-nerve growth factor or with the adenylate cyclase activator forskolin was observed. To assess the validity of the PC12-cell model system, we examined the effect of leptin administration on the gene transcription of STAT-3, MT-II, Fnk and PAP I in vivo. Leptin treatment of leptin-deficient ob/ob mice increased the STAT-3, SOCS-3, MT-II and Fnk mRNA, and MT-I protein levels in liver, whereas, in jejunum, expression of PAP I mRNA was down-regulated. Furthermore, administration of leptin to starved wild-type mice enhanced the expression of MT-II and Fnk mRNA in liver, but decreased MT-II and PAP I mRNA expression in jejunum. These findings may help to explain the obese phenotype observed in some colonies of MT-I- and MT-II-null mice and/or the observation that leptin protects against tumour-necrosis-factor toxicity in vivo.

    AB - Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation of the leptin receptor. On the basis of kinetic studies, two distinct gene sets could be discerned: signal transducer and activator of transciption-3 (STAT-3), suppressor of cytokine signalling-3 (SOCS-3), MT-II (metallothionein-II), the serine/threonine kinase fibroblast-growth-factor-inducible kinase (Fnk) and modulator recognition factor (MRF-1), which are immediate early response genes, and pancreatitis-associated protein I (PAP I), squalene epoxidase, uridine diphosphate glucuronosyltransferase and annexin VIII, which are late induced target genes. At late time points a strong co-stimulation with beta-nerve growth factor or with the adenylate cyclase activator forskolin was observed. To assess the validity of the PC12-cell model system, we examined the effect of leptin administration on the gene transcription of STAT-3, MT-II, Fnk and PAP I in vivo. Leptin treatment of leptin-deficient ob/ob mice increased the STAT-3, SOCS-3, MT-II and Fnk mRNA, and MT-I protein levels in liver, whereas, in jejunum, expression of PAP I mRNA was down-regulated. Furthermore, administration of leptin to starved wild-type mice enhanced the expression of MT-II and Fnk mRNA in liver, but decreased MT-II and PAP I mRNA expression in jejunum. These findings may help to explain the obese phenotype observed in some colonies of MT-I- and MT-II-null mice and/or the observation that leptin protects against tumour-necrosis-factor toxicity in vivo.

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    KW - metallothionein

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    KW - MESSENGER-RNA EXPRESSION

    KW - METALLOTHIONEIN-II GENES

    KW - IN-SITU HYBRIDIZATION

    KW - OBESE GENE

    KW - BODY-WEIGHT

    KW - PERIPHERAL-TISSUES

    KW - NEUROPEPTIDE-Y

    KW - DIABETIC MICE

    KW - DB/DB MICE

    M3 - Article

    VL - 348

    SP - 55

    EP - 61

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    ER -