title: TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity.
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 mug/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 beta2-AR (beta2 adrenergic receptor) and white adipose tissue (WAT) PPAR-delta (peroxisome proliferator-activated receptor delta), beta3-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.
authors.affiliation: Institute of Neuroscience, Consiglio Nazionale delle Ricerche, 00143 Rome, Italy. bartolomucci@biol.unipr.it
authors.forename: A
authors.initials: A
authors.lastname: Bartolomucci
authors.forename: G
authors.initials: G
authors.lastname: La Corte
authors.forename: R
authors.initials: R
authors.lastname: Possenti
authors.forename: V
authors.initials: V
authors.lastname: Locatelli
authors.forename: A E
authors.initials: AE
authors.lastname: Rigamonti
authors.forename: A
authors.initials: A
authors.lastname: Torsello
authors.forename: E
authors.initials: E
authors.lastname: Bresciani
authors.forename: I
authors.initials: I
authors.lastname: Bulgarelli
authors.forename: R
authors.initials: R
authors.lastname: Rizzi
authors.forename: F
authors.initials: F
authors.lastname: Pavone
authors.forename: F R
authors.initials: FR
authors.lastname: D'Amato
authors.forename: C
authors.initials: C
authors.lastname: Severini
authors.forename: G
authors.initials: G
authors.lastname: Mignogna
authors.forename: A
authors.initials: A
authors.lastname: Giorgi
authors.forename: M E
authors.initials: ME
authors.lastname: Schininà
authors.forename: G
authors.initials: G
authors.lastname: Elia
authors.forename: C
authors.initials: C
authors.lastname: Brancia
authors.forename: G-L
authors.initials: GL
authors.lastname: Ferri
authors.forename: R
authors.initials: R
authors.lastname: Conti
authors.forename: B
authors.initials: B
authors.lastname: Ciani
authors.forename: T
authors.initials: T
authors.lastname: Pascucci
authors.forename: G
authors.initials: G
authors.lastname: Dell'Omo
authors.forename: E E
authors.initials: EE
authors.lastname: Muller
authors.forename: A
authors.initials: A
authors.lastname: Levi
authors.forename: A
authors.initials: A
authors.lastname: Moles
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D004032:Diet / Q000009:adverse effects*; D004734:Energy Metabolism; D054439:Ghrelin; D005951:Glucose Tolerance Test; D007473:Ion Channels / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics; D009414:Nerve Growth Factors; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced*; D047495:PPAR gamma / Q000235:genetics; D036361:Peptide Hormones / Q000097:blood; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000235:genetics
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D047495:PPAR gamma; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C512697:Vgf protein, mouse; C062040:Vgf protein, rat