Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation
Peripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, incl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.864925/full |
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| author | Magdalena Blaszkiewicz Gilian Gunsch Jake W. Willows Miranda L. Gardner Miranda L. Gardner Jesse A. Sepeda Andrew R. Sas Kristy L. Townsend |
| author_facet | Magdalena Blaszkiewicz Gilian Gunsch Jake W. Willows Miranda L. Gardner Miranda L. Gardner Jesse A. Sepeda Andrew R. Sas Kristy L. Townsend |
| author_sort | Magdalena Blaszkiewicz |
| collection | DOAJ |
| description | Peripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, including subcutaneous white adipose tissue (scWAT). However, in scWAT, their functions beyond degrading norepinephrine in an obese state remain largely unexplored. We previously reported that a myeloid-lineage knockout (KO) of brain-derived neurotrophic factor (BDNF) resulted in decreased innervation of scWAT, accompanied by an inability to brown scWAT after cold stimulation, and increased adiposity after a high-fat diet. These data underscored that adipose tissue neuroimmune cells support the peripheral nerve supply to adipose and impact the tissue’s metabolic functions. We also reported that a subset of myeloid-lineage monocyte/macrophages (Ly6c+CCR2+Cx3cr1+) is recruited to scWAT in response to cold, a process known to increase neurite density in adipose and promote metabolically healthy processes. These cold-induced neuroimmune cells (CINCs) also expressed BDNF. Here we performed RNAseq on CINCs from cold-exposed and room temperature-housed mice, which revealed a striking and coordinated differential expression of numerous genes involved in neuronal function, including neurotrophin signaling and axonal guidance, further supporting that CINCs fulfill a nerve-supporting role in adipose. The increased expression of leukocyte transendothelial migration genes in cold-stimulated CINCs also confirms prior evidence that they are recruited to scWAT and are not tissue resident. We now provide whole-depot imaging of scWAT from LysM-BDNF KO mice, revealing a striking reduction of innervation across the depot fitting with their reduced energy expenditure phenotype. By contrast, Cx3cr1-BDNF KO mice (a macrophage subset of LysM+ cells) exhibited increased thermogenesis and energy expenditure, with compensatory increased food intake and no change in adiposity or body weight. While these KO mice also exhibit a significantly reduced innervation of scWAT, especially around the subiliac lymph node, they displayed an increase in small fiber sympathetic neurite branching, which may underlie their increased thermogenesis. We propose a homeostatic role of scWAT myeloid-lineage neuroimmune cells together in nerve maintenance and neuro-adipose regulation of energy expenditure. |
| first_indexed | 2024-04-12T13:57:22Z |
| format | Article |
| id | doaj.art-f8242b9540784c96b5f5a7ab201e3f4f |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T13:57:22Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-f8242b9540784c96b5f5a7ab201e3f4f2022-12-22T03:30:19ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.864925864925Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose InnervationMagdalena Blaszkiewicz0Gilian Gunsch1Jake W. Willows2Miranda L. Gardner3Miranda L. Gardner4Jesse A. Sepeda5Andrew R. Sas6Kristy L. Townsend7Neurobiology and Energy Balance Laboratory, Department of Neurological Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesNeurobiology and Energy Balance Laboratory, Department of Neurological Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesNeurobiology and Energy Balance Laboratory, Department of Neurological Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesCampus Chemical Instrument Center, Mass Spectrometry and Proteomics Facility, The Ohio State University, Columbus, OH, United StatesDepartment of Neurology, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesDepartment of Neurology, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesNeurobiology and Energy Balance Laboratory, Department of Neurological Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, United StatesPeripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, including subcutaneous white adipose tissue (scWAT). However, in scWAT, their functions beyond degrading norepinephrine in an obese state remain largely unexplored. We previously reported that a myeloid-lineage knockout (KO) of brain-derived neurotrophic factor (BDNF) resulted in decreased innervation of scWAT, accompanied by an inability to brown scWAT after cold stimulation, and increased adiposity after a high-fat diet. These data underscored that adipose tissue neuroimmune cells support the peripheral nerve supply to adipose and impact the tissue’s metabolic functions. We also reported that a subset of myeloid-lineage monocyte/macrophages (Ly6c+CCR2+Cx3cr1+) is recruited to scWAT in response to cold, a process known to increase neurite density in adipose and promote metabolically healthy processes. These cold-induced neuroimmune cells (CINCs) also expressed BDNF. Here we performed RNAseq on CINCs from cold-exposed and room temperature-housed mice, which revealed a striking and coordinated differential expression of numerous genes involved in neuronal function, including neurotrophin signaling and axonal guidance, further supporting that CINCs fulfill a nerve-supporting role in adipose. The increased expression of leukocyte transendothelial migration genes in cold-stimulated CINCs also confirms prior evidence that they are recruited to scWAT and are not tissue resident. We now provide whole-depot imaging of scWAT from LysM-BDNF KO mice, revealing a striking reduction of innervation across the depot fitting with their reduced energy expenditure phenotype. By contrast, Cx3cr1-BDNF KO mice (a macrophage subset of LysM+ cells) exhibited increased thermogenesis and energy expenditure, with compensatory increased food intake and no change in adiposity or body weight. While these KO mice also exhibit a significantly reduced innervation of scWAT, especially around the subiliac lymph node, they displayed an increase in small fiber sympathetic neurite branching, which may underlie their increased thermogenesis. We propose a homeostatic role of scWAT myeloid-lineage neuroimmune cells together in nerve maintenance and neuro-adipose regulation of energy expenditure.https://www.frontiersin.org/articles/10.3389/fendo.2022.864925/fullscWATBDNFenergy expenditureneuroimmuneneural plasticityCINCs |
| spellingShingle | Magdalena Blaszkiewicz Gilian Gunsch Jake W. Willows Miranda L. Gardner Miranda L. Gardner Jesse A. Sepeda Andrew R. Sas Kristy L. Townsend Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation Frontiers in Endocrinology scWAT BDNF energy expenditure neuroimmune neural plasticity CINCs |
| title | Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation |
| title_full | Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation |
| title_fullStr | Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation |
| title_full_unstemmed | Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation |
| title_short | Adipose Tissue Myeloid-Lineage Neuroimmune Cells Express Genes Important for Neural Plasticity and Regulate Adipose Innervation |
| title_sort | adipose tissue myeloid lineage neuroimmune cells express genes important for neural plasticity and regulate adipose innervation |
| topic | scWAT BDNF energy expenditure neuroimmune neural plasticity CINCs |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.864925/full |
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