title: Leptin fragments induce Fos immunoreactivity in rat hypothalamus.
abstract: Leptin presents an important role in energy balance and neuroendocrine control in mammals. In an attempt to identify regions of the leptin molecule responsible for its bioactivity, we have synthesized six peptides based on the protein three-dimensional structure. Fragments were synthesized by the solid-phase methodology, purified by reverse-phase high-performance liquid chromatography (RP-HPLC), and characterized by liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS). They were injected intravenously and their ability to induce Fos immunoreactivity (Fos-ir) in rat hypothalamus was compared with that of the recombinant human leptin and saline. Fragment Ac-[Ser117]Lep116-140-NH2 (V) induced Fos-ir in hypothalamic nuclei that express leptin receptor long form. No similar ability was observed for the other five fragments. To investigate whether Fos-ir was induced in the same neuronal group activated by leptin, we proceeded with a dual-label immunohistochemistry for cocaine- and amphetamine-regulated transcript (CART), a neuropeptide related to leptin action in rat hypothalamus. We found that Ac-[Ser117]Lep116-140-NH2 (V) differentially activates CART neurons through the rostrocaudal extension of the arcuate nucleus. These results suggest that this fragment acts in the same group of neurons that mediate leptin response. This approach may offer the basis for the development of leptin-related compounds, having potential application in human or veterinary medicine.
authors.affiliation: Department of Biophysics, Federal University of São Paulo (UNIFESP), São Paulo 04044-020, Brazil.
authors.forename: Vani X
authors.initials: VX
authors.lastname: Oliveira
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Fázio
authors.forename: M Terêsa M
authors.initials: MT
authors.lastname: Miranda
authors.forename: Joelcimar M
authors.initials: JM
authors.lastname: da Silva
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
mesh_terms: D000818:Animals; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D020738:Leptin; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein