The involvement of neuroimmune cells in adipose innervation
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Molecular Medicine
Open Access
RESEARCH ARTICLE
The involvement of neuroimmune cells in adipose innervation Magdalena Blaszkiewicz1,2, Elizabeth Wood1, Sigi Koizar1, Jake Willows1, Ryan Anderson1, Yu‑Hua Tseng3, James Godwin4,5 and Kristy L. Townsend1,2,6*
Abstract Background: Innervation 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 com‑ munication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell num‑ ber, 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 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 innerva‑ tion. We previously demonstrated that adipose SVF secretes brain derived neurotrophic factor (BDNF). Methods: We now show that deletion of this neurotrophic factor from the myeloid lineage of immune cells 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. Results: We 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. This subset of myeloid lineage cells also clearly interacted with peripheral nerves in the scWAT and were therefore considered neuroimmune cells. Conclusions: We propose that these myeloid lineage, 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. Keywords: Innervation, White adipose tissue (WAT), Energy expenditure, Browning, CINCs, Cold-induced neuroimmune cells, BDNF, Monocyte/macrophage Introduction In order for the central nervous system (CNS) to regulate functions of distal organs and tissues, peripheral nervous system (PNS) innervation needs to be maintained and properly coordinated. It has been demonstrated *Correspondence: [email protected] 6 The Ohio State University, 1014 Biomedical Research Tower, 460 W 12th Ave, Columbus, OH 43210, USA Full list of author information is available at the end of the article
repeatedly that loss of innervation of the adipose organ (by surgical or chemical means) led to dysfunction of the tissue and disruption to whole body energy homeostasis. Denervation of brown adipose tissue (BAT) greatly impairs the energy expending process of adaptive therm
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