title: Ciliary neurotrophic factor influences endocrine adipocyte function: inhibition of leptin via PI 3-kinase.
abstract: Ciliary neurotrophic factor (CNTF), originally known for its involvement in the modulation of neuronal growth, has been discovered to exert anorexigenic effects and is currently being investigated in clinical studies for the treatment of obesity and insulin resistance. This neuropeptide acts on the central nervous system. However, we have recently demonstrated direct peripheral effects on adipocyte signalling and thermogenesis. Given the emerging endocrine role of adipose tissue in the regulation of energy homeostasis and insulin resistance, we investigated potential effects of CNTF on leptin expression and secretion. Our study demonstrates a direct inhibition of leptin expression and secretion by acute and chronic CNTF treatment. Furthermore, we demonstrate a differentiation- and Janus kinase 2 (JAK2)-independent, but phosphatidylinositol 3-kinase-dependent signalling pathway mediating this negative effect. These results provide novel evidence for a role of CNTF in the selective modulation of adipocyte endocrine function which may have important implications for the regulation of energy homeostasis.
authors.affiliation: Department of Internal Medicine I, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Ott
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
authors.forename: Britta
authors.initials: B
authors.lastname: Meier
authors.forename: Andreas
authors.initials: A
authors.lastname: Dalski
authors.forename: Daniel
authors.initials: D
authors.lastname: Kraus
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gettys
authors.forename: Nina
authors.initials: N
authors.lastname: Perwitz
authors.forename: Johannes
authors.initials: J
authors.lastname: Klein
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D004703:Endocrine System / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
chemical_list: D002867:Chromones; D020934:Ciliary Neurotrophic Factor; D020738:Leptin; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one