1. Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21
- Author
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Monia Manieri, Federico Quaini, Antonio Giordano, Paolo Govoni, Corrado Ghè, Anna Moles, Maureen S. Riedl, Gallia Graiani, Lucy Vulchanova, Pamela Petrocchi, Saverio Cinti, Elena Bresciani, I. Bulgarelli, Alessandro Bartolomucci, Giampiero Muccioli, Aderville Cabassi, Roberta Possenti, Andrea Levi, Stefano Parmigiani, Antonio Torsello, Valentina Sanghez, Vittorio Locatelli, Andrea Frontini, Jørgen Petersen, Paola Palanza, Bjarne Due Larsen, Cheryl Cero, Possenti, R, Muccioli, G, Petrocchi, P, Cero, C, Cabassi, A, Vulchanova, L, Riedl, M, Manieri, M, Frontini, A, Giordano, A, Cinti, S, Govoni, P, Graiani, G, Quaini, F, Ghè, C, Bresciani, E, Bulgarelli, I, Torsello, A, Locatelli, V, Sanghez, V, Larsen, B, Petersen, J, Palanza, P, Parmigiani, S, Moles, A, Levi, A, and Bartolomucci, A
- Subjects
Male ,medicine.medical_specialty ,Adipose tissue ,Peptide ,Receptors, Cell Surface ,White adipose tissue ,Biology ,adipocyte ,Settore BIO/09 ,Biochemistry ,sympathetic nervous system VGF ,chemistry.chemical_compound ,Mice ,In vivo ,Internal medicine ,Adipocyte ,medicine ,Adipocytes ,Lipolysis ,Animals ,Nerve Growth Factors ,Obesity ,Receptor ,BIO/14 - FARMACOLOGIA ,Molecular Biology ,chemistry.chemical_classification ,granin-derived peptide ,TLQP-21 ,Neuropeptides ,²-adrenergic receptor ,VGF ,Cell Biology ,Dietary Fats ,Peptide Fragments ,adipose tissue ,Protein Transport ,Endocrinology ,chemistry ,Body Composition ,NIH 3T3 Cells ,Ex vivo ,Protein Binding - 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 receptormediated 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 obesityassociated metabolic complications. © The Authors Journal compilation © 2012 Biochemical Society.
- Published
- 2012