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.
Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21 / R. Possenti; G. Muccioli; P. Petrocchi; C. Cero; A. Cabassi; L. Vulchanova; M.S. Riedl; M. Manieri; A. Frontini; A. Giordano; S. Cinti; P. Govoni; G. Graiani; F. Quaini; C. Ghe; E. Bresciani; I. Bulgarelli; A. Torsello; V. Locatelli; V. Sanghez; B.D. Larsen; J.S. Petersen; P. Palanza; S. Parmigiani; A. Moles; A. Levi; A. Bartolomucci. - In: BIOCHEMICAL JOURNAL. - ISSN 0264-6021. - 441(2012), pp. 511-522. [10.1042/BJ20111165]