Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21.

Abstract

The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve-adipocytes interaction might prove to be a novel approach for the treatment of obesity-associated metabolic complications.

• Authors: Roberta Possenti, Giampiero Muccioli, Pamela Petrocchi, Cheryl Cero, Aderville Cabassi, Lucy Vulchanova, Maureen S Riedl, Monia Manieri, Andrea Frontini, Antonio Giordano, Saverio Cinti, Paolo Govoni, Gallia Graiani, Federico Quaini, Corrado Ghè, Elena Bresciani, Ilaria Bulgarelli, Antonio Torsello, Vittorio Locatelli, Valentina Sanghez, Bjarne D Larsen, Jorgen S Petersen, Paola Palanza, Stefano Parmigiani, Anna Moles, Andrea Levi, Alessandro Bartolomucci
• Journal: The Biochemical journal (Biochem J) Vol. 441 Issue 1 Pg. 511-22 (Jan 01 2012) ISSN: 1470-8728 [Electronic] England
• PMID: 21880012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Nerve Growth Factors
• Neuropeptides
• Peptide Fragments
• Receptors, Cell Surface
• TLQP-21 peptide
• Vgf protein, mouse

Topics

• Adipocytes (cytology, drug effects)
• Animals
• Body Composition
• Dietary Fats (adverse effects, metabolism)
• Male
• Mice
• NIH 3T3 Cells
• Nerve Growth Factors
• Neuropeptides (metabolism)
• Obesity (chemically induced, metabolism)
• Peptide Fragments (pharmacology)
• Protein Binding
• Protein Transport
• Receptors, Cell Surface