Adipocyte-derived angiopoietin-1 supports neurite outgrowth and synaptogenesis of sensory neurons.
Sensory and sympathetic innervation of the white fat tissue (WAT) contributes to lipolysis. In addition, both fiber types adapt in density to weight gain and loss. Because these findings are indicative for a tight control of nerve fiber plasticity by adipokines, we tested whether adipocytes control neurite growth of sensory neurons through angiopoietin-1 (Ang-1). We further considered initial hints that Ang-1-induced neuritogenesis involves transactivation of the high-affinity nerve growth factor (NGF) receptor trkA. Coculturing dorsal root ganglion (DRG) cells with 3T3-L1 adipocytes supported neurite outgrowth. These neurotrophic effects were associated with the increased expression of Ang-1 (presumably in adipocytes) as well as of trkA. The effects were abolished upon inactivating Ang-1 in culture with selective antibodies. Likewise, neurite outgrowth was impaired in the presence of inactivating NGF antibodies as well as upon inhibition of the NGF high-affinity trkA receptor with the antagonist K252a, indicating a tight cooperation of Ang-1 and NGF in the control of neuritogenesis. DRG-adipipocyte cocultures were further used to establish whether sensory neurons would form synaptic contacts with adipocytes. Electron microscopy demonstrated that cultured sensory neurons develop predominantly neuroneuronal synapses but seem to affect adipocytes by synapses en passant. Comparably to the case for neuritogenesis, expression of the presynaptic protein synaptophysin as well of the postsynaptic protein PSD-95 correlated with Ang-1 levels in culture. It is concluded that adipocyte-secreted Ang-1 supports neurite outgrowth, which is involved in synaptogenesis. The novel function of Ang-1 appears to play a physiological role in WAT plasticity.
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Joanna
J
Kosacka
Marcin
M
Nowicki
Johannes
J
Kacza
Jürgen
J
Borlak
Jürgen
J
Engele
Katharina
K
Spanel-Borowski
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000294:innervation / Q000378:metabolism; D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques; D000076122:Disks Large Homolog 4 Protein; D005727:Ganglia, Spinal / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011920:Rats, Inbred WF; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
D042683:Angiopoietin-1; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016708:Synaptophysin; D020932:Nerve Growth Factor; D020917:Receptor, trkA