title: Acute anorexigenic action of leptin in rainbow trout is mediated by the hypothalamic Pi3k pathway.
abstract: Leptin (Lep) is an anorexigenic hormone and regulates appetite-related neuropeptides in mammals. A number of neuropeptides have also been linked to appetite regulation in teleost fish, but Lep signaling activation and effects on appetite-regulating neurons are poorly elucidated in early vertebrates. This study uses cellular, tissue and organismal approaches to elucidate the acute, central Lep action in rainbow trout. The results demonstrate that Lep activates phosphorylation of protein kinase B (Akt) and signal transducer and activator of transcription 3 in rainbow trout hypothalamus-derived cells, and that the phosphatidylinositol-3-kinase (Pi3k) inhibitor LY294002 can suppress the Lep-induced Akt phosphorylation. Intracerebroventricular (ICV) Lep administration strongly suppresses food intake at the doses of 0.05 and 0.5 µg Lep fish(-1) At low dose, Lep stimulates hypothalamic transcription of anorexigenic cocaine- and amphetamine-regulated transcript (Cart) and orexigenic neuropeptide Y. At high dose, Lep stimulates hypothalamic transcription of anorexigenic proopiomelanocortin (Pomc) A1, A2, and B, while coinjection with LY294002 reverses this upregulation. The data suggest that the anorexigenic action of Lep in rainbow trout is mediated through stimulation of the anorexigenic neuropeptides Pomc and Cart. Furthermore, ICV Lep treatment increases phosphor-Akt-immunoreactive cells in the nucleus lateralis tuberis, periventricular zone along infundibulum, and lateral recess surrounded by nucleus anterior tuberis, while LY294002 inhibits this effect. Lep receptor-immunoreactive cells are also predominant in these regions. These results demonstrate that Lep activates the Pi3k-Akt pathway in the lateral tuberal hypothalamus of rainbow trout for acute appetite regulation, indicating the conservation of anorexigenic Lep action in the mediobasal hypothalamus.
authors.affiliation: Fish Endocrinology LaboratoryDepartment of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ningping
authors.initials: N
authors.lastname: Gong
authors.affiliation: Fish Endocrinology LaboratoryDepartment of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jönsson
authors.affiliation: Fish Endocrinology LaboratoryDepartment of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden thrandur.bjornsson@bioenv.gu.se.
authors.forename: Björn Thrandur
authors.initials: BT
authors.lastname: Björnsson
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001067:Appetite Depressants; D020738:Leptin; D009479:Neuropeptides; D050796:STAT3 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Pi3k-Akt; appetite; leptin; neuropeptide; teleost fish