Leptin-mediated gene-induction

US7291458B2 · kind B2 · utility

Assignee

• VLAAMS INTERUNIVERSITAIR INSTITUUT VOOR BIOTECHNOLOGIE VZW · BE

Inventors

• Daniel Broekaert · Lievegem, BE
• Joel Vandekerckhove · Loppem, BE
• Annick Verhee · Lichtervelde, BE
• Wim Waelput · Sint-Niklaas, BE
• Jan Tavernier · Balegem, BE

Key dates

• Filing date: Sep 4, 2002
• Grant date: Nov 6, 2007
• Expiry date: Jan 26, 2024

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P43/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin co-stimulatory effect was observed. It is also demonstrated that leptin modulates in vivo expression of MT-II, Fnk and Pancreatitis Associated Protein I genes.