The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 μg/day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue β2-AR (β2 adrenergic receptor) and white adipose tissue (WAT) PPAR-δ (peroxisome proliterator-activated receptor δ), β3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity / A. Bartolomucci, G. La Corte, R. Possenti, V. Locatelli, A.E. Rigamonti, A. Torsello, E. Bresciani, I. Bulgarelli, R. Rizzi, F. Pavone, F.R. D'Amato, C. Severini, G. Mignogna, A. Giorgi, M.E. Schininà, G. Elia, C. Brancia, G. Ferri, R. Conti, B. Ciani, T. Pascucci, G. Dell'Omo, E.E. Muller, A. Levi, A. Moles. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 103:39(2006 Sep 26), pp. 14584-14589. [10.1073/pnas.0606102103]

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity

A. Bartolomucci
;
A.E. Rigamonti;I. Bulgarelli;R. Rizzi;G. Dell'Omo;
2006

Abstract

The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 μg/day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue β2-AR (β2 adrenergic receptor) and white adipose tissue (WAT) PPAR-δ (peroxisome proliterator-activated receptor δ), β3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.
β adrenergic receptor; autonomic nervous system; MALDI-TOF; neuropeptide; peroxisome proliferator-activated receptor δ; adipose tissue, brown; animals; blood glucose; diet; Ghrelin; glucose tolerance test; Ion Channels; Leptin; male; mice; mitochondrial proteins; neuropeptides; obesity; PPAR gamma; peptide hormones; peptides; RNA, messenger; rats; receptors, adrenergic, beta; spectrometry, mass, Matrix-Assisted Laser Desorption-Ionization; triglycerides; Uncoupling Protein 1; Up-Regulation; energy metabolism; genetics; multidisciplinary
Settore BIO/14 - Farmacologia
26-set-2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/502438
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