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

    52 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.