Myeloid-secreted BDNF maintains innervation of inguinal adipose in male mice

Blaszkiewicz, M.; Wood, E.; Koizar, S.; Willows, J. W.; Cao, L.; Huang, W.; Godwin, J.; Townsend, K.

doi:10.1101/787234

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bioRxiv · 10.1101/787234

Myeloid-secreted BDNF maintains innervation of inguinal adipose in male mice

Blaszkiewicz, M.·Wood, E.·Koizar, S.·Willows, J. W.·Cao, L.·Huang, W.·Godwin, J.·Townsend, K.

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Abstract

BackgroundInnervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and browning of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF). MethodsWe now show that deletion of this neurotrophic factor from the myeloid lineage led to a genetic denervation of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. ResultsWe and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF. ConclusionsWe propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

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Blaszkiewicz, M., Wood, E., Koizar, S., Willows, J. W., Cao, L., Huang, W., Godwin, J., Townsend, K.. 2019-09-30. Myeloid-secreted BDNF maintains innervation of inguinal adipose in male mice. https://doi.org/10.1101/787234

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