Direct effects of ciliary neurotrophic factor on brown adipocytes: evidence for a role in peripheral regulation of energy homeostasis.
Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal growth. Recently, central anorexigenic effects of this cytokine have been characterized. However, peripheral effects on tissues that actively contribute to the regulation of energy homeostasis have not been described. Here, we report direct potent and selective effects of CNTF on growth factor and metabolic signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6 kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are separately acting, main intermediates for inducing mitogen-activated protein (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic induction of uncoupling protein-1. Thus, these results demonstrate direct effects of CNTF on adipose tissue signalling and metabolism and suggest a novel role for this cytokine in the peripheral regulation of energy homeostasis.
Ott
V
V
Department of Internal Medicine I, Medical University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Fasshauer
M
M
Dalski
A
A
Klein
H H
HH
Klein
J
J
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004734:Energy Metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006706:Homeostasis; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D019950:Mitogen-Activated Protein Kinase 1; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D022702:Receptors, Adrenergic, beta-3; D019893:Ribosomal Protein S6 Kinases; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000071256:Uncoupling Protein 1; C494087:Stat3 protein, mouse; C000604372:Ucp1 protein, mouse