Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit
Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1,2,3,4. Nevertheless, it is unclear whether neuronal...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2021
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| _version_ | 1826276854759161856 |
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| author | Cardoso, F Klein Wolterink, RGJ Godinho-Silva, C Domingues, RG Ribeiro, H da Silva, JA Mahú, I Domingos, AI Veiga-Fernandes, H |
| author_facet | Cardoso, F Klein Wolterink, RGJ Godinho-Silva, C Domingues, RG Ribeiro, H da Silva, JA Mahú, I Domingos, AI Veiga-Fernandes, H |
| author_sort | Cardoso, F |
| collection | OXFORD |
| description | Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1,2,3,4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain–body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain–adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the β2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.
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| first_indexed | 2024-03-06T23:20:06Z |
| format | Journal article |
| id | oxford-uuid:68707e08-ddf9-4b84-af78-336f1adc2462 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:20:06Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:68707e08-ddf9-4b84-af78-336f1adc24622022-03-26T18:44:56ZNeuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuitJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:68707e08-ddf9-4b84-af78-336f1adc2462EnglishSymplectic ElementsSpringer Nature2021Cardoso, FKlein Wolterink, RGJGodinho-Silva, CDomingues, RGRibeiro, Hda Silva, JAMahú, IDomingos, AIVeiga-Fernandes, HSignals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1,2,3,4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain–body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain–adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the β2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity. |
| spellingShingle | Cardoso, F Klein Wolterink, RGJ Godinho-Silva, C Domingues, RG Ribeiro, H da Silva, JA Mahú, I Domingos, AI Veiga-Fernandes, H Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title | Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title_full | Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title_fullStr | Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title_full_unstemmed | Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title_short | Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit |
| title_sort | neuro mesenchymal units control ilc2 and obesity via a brain adipose circuit |
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