title: 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: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors: Roberta
authors: R
authors: Possenti
authors: Giampiero
authors: G
authors: Muccioli
authors: Pamela
authors: P
authors: Petrocchi
authors: Cheryl
authors: C
authors: Cero
authors: Aderville
authors: A
authors: Cabassi
authors: Lucy
authors: L
authors: Vulchanova
authors: Maureen S
authors: MS
authors: Riedl
authors: Monia
authors: M
authors: Manieri
authors: Andrea
authors: A
authors: Frontini
authors: Antonio
authors: A
authors: Giordano
authors: Saverio
authors: S
authors: Cinti
authors: Paolo
authors: P
authors: Govoni
authors: Gallia
authors: G
authors: Graiani
authors: Federico
authors: F
authors: Quaini
authors: Corrado
authors: C
authors: Ghè
authors: Elena
authors: E
authors: Bresciani
authors: Ilaria
authors: I
authors: Bulgarelli
authors: Antonio
authors: A
authors: Torsello
authors: Vittorio
authors: V
authors: Locatelli
authors: Valentina
authors: V
authors: Sanghez
authors: Bjarne D
authors: BD
authors: Larsen
authors: Jorgen S
authors: JS
authors: Petersen
authors: Paola
authors: P
authors: Palanza
authors: Stefano
authors: S
authors: Parmigiani
authors: Anna
authors: A
authors: Moles
authors: Andrea
authors: A
authors: Levi
authors: Alessandro
authors: A
authors: Bartolomucci
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001823:Body Composition; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D009414:Nerve Growth Factors; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding; D021381:Protein Transport; D011956:Receptors, Cell Surface
chemical_list: D004041:Dietary Fats; D009414:Nerve Growth Factors; D009479:Neuropeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C522412:TLQP-21 peptide; C512697:Vgf protein, mouse