The involvement of neuroimmune cells in adipose innervation
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 communication through both sympathetic efferent and sensory afferent nerves h...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-020-00254-3 |
| _version_ | 1818352655675686912 |
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| author | Magdalena Blaszkiewicz Elizabeth Wood Sigi Koizar Jake Willows Ryan Anderson Yu-Hua Tseng James Godwin Kristy L. Townsend |
| author_facet | Magdalena Blaszkiewicz Elizabeth Wood Sigi Koizar Jake Willows Ryan Anderson Yu-Hua Tseng James Godwin Kristy L. Townsend |
| author_sort | Magdalena Blaszkiewicz |
| collection | DOAJ |
| description | 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 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 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 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. |
| first_indexed | 2024-12-13T18:57:05Z |
| format | Article |
| id | doaj.art-05a03f18f6e14436bfa8dd5b280af5f2 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-13T18:57:05Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-05a03f18f6e14436bfa8dd5b280af5f22022-12-21T23:34:46ZengBMCMolecular Medicine1076-15511528-36582020-12-0126111910.1186/s10020-020-00254-3The involvement of neuroimmune cells in adipose innervationMagdalena Blaszkiewicz0Elizabeth Wood1Sigi Koizar2Jake Willows3Ryan Anderson4Yu-Hua Tseng5James Godwin6Kristy L. Townsend7School of Biology and Ecology, University of MaineSchool of Biology and Ecology, University of MaineSchool of Biology and Ecology, University of MaineSchool of Biology and Ecology, University of MaineSchool of Biology and Ecology, University of MaineJoslin Diabetes Center, Harvard Medical SchoolJackson LaboratorySchool of Biology and Ecology, University of MaineAbstract 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 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 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 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.https://doi.org/10.1186/s10020-020-00254-3InnervationWhite adipose tissue (WAT)Energy expenditureBrowningCINCsCold-induced neuroimmune cells |
| spellingShingle | Magdalena Blaszkiewicz Elizabeth Wood Sigi Koizar Jake Willows Ryan Anderson Yu-Hua Tseng James Godwin Kristy L. Townsend The involvement of neuroimmune cells in adipose innervation Molecular Medicine Innervation White adipose tissue (WAT) Energy expenditure Browning CINCs Cold-induced neuroimmune cells |
| title | The involvement of neuroimmune cells in adipose innervation |
| title_full | The involvement of neuroimmune cells in adipose innervation |
| title_fullStr | The involvement of neuroimmune cells in adipose innervation |
| title_full_unstemmed | The involvement of neuroimmune cells in adipose innervation |
| title_short | The involvement of neuroimmune cells in adipose innervation |
| title_sort | involvement of neuroimmune cells in adipose innervation |
| topic | Innervation White adipose tissue (WAT) Energy expenditure Browning CINCs Cold-induced neuroimmune cells |
| url | https://doi.org/10.1186/s10020-020-00254-3 |
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