Elisa Duregotti, Christina M. Reumiller, Ursula Mayr, Maria Hasman, Lukas E. Schmidt, Sean A. Burnap, Konstantinos Theofilatos, Javier Barallobre-Barreiro, Arne Beran, Maria Grandoch, Alessandro Viviano, Marjan Jahangiri, Manuel Mayr
| Original language | English |
|---|
| Article number | 7269 |
|---|
| Journal | Nature Communications |
|---|
| Volume | 13 |
|---|
| Issue number | 1 |
|---|
| DOIs | |
|---|
| Published | Dec 2022 |
|---|
| Additional links | |
|---|
Funding Information:
We sincerely thank the Wohl Cellular Imaging Centre (King’s College London) where the confocal microscopy images were acquired. We are also grateful to Dr. Matthew White for helping us setting up primary sympathetic neuronal cultures. M.M. is a British Heart Foundation (BHF) Chair Holder (CH/16/3/32406) with BHF programme grant support (RG/16/14/32397, RG/F/21/110053). M.M. received support from the BHF Centre for Vascular Regeneration with Edinburgh/Bristol (RM/17/3/33381). M.M. is also supported by the Leducq Foundation (“PlaqOmics”, 18CVD02) and VASCage-C (Research Centre on Vascular Ageing and Stroke), an R&D K-Centre of the Austrian Research Promotion Agency (COMET program—Competence Centres for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol, Salzburg and Vienna with the grant number FSG 868624. This study was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Grant No. 236177352—SFB 1116, TPB10; GRK2576 vivid, P2 (M.G.).
Funding Information:
We sincerely thank the Wohl Cellular Imaging Centre (King’s College London) where the confocal microscopy images were acquired. We are also grateful to Dr. Matthew White for helping us setting up primary sympathetic neuronal cultures. M.M. is a British Heart Foundation (BHF) Chair Holder (CH/16/3/32406) with BHF programme grant support (RG/16/14/32397, RG/F/21/110053). M.M. received support from the BHF Centre for Vascular Regeneration with Edinburgh/Bristol (RM/17/3/33381). M.M. is also supported by the Leducq Foundation (“PlaqOmics”, 18CVD02) and VASCage-C (Research Centre on Vascular Ageing and Stroke), an R&D K-Centre of the Austrian Research Promotion Agency (COMET program—Competence Centres for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol, Salzburg and Vienna with the grant number FSG 868624. This study was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Grant No. 236177352—SFB 1116, TPB10; GRK2576 vivid, P2 (M.G.).
Publisher Copyright:
© 2022, The Author(s).
While the endocrine function of white adipose tissue has been extensively explored, comparatively little is known about the secretory activity of less-investigated fat depots. Here, we use proteomics to compare the secretory profiles of male murine perivascular depots with those of canonical white and brown fat. Perivascular secretomes show enrichment for neuronal cell-adhesion molecules, reflecting a higher content of intra-parenchymal sympathetic projections compared to other adipose depots. The sympathetic innervation is reduced in the perivascular fat of obese (ob/ob) male mice, as well as in the epicardial fat of patients with obesity. Degeneration of sympathetic neurites is observed in presence of conditioned media of fat explants from ob/ob mice, that show reduced secretion of neuronal growth regulator 1. Supplementation of neuronal growth regulator 1 reverses this neurodegenerative effect, unveiling a neurotrophic role for this protein previously identified as a locus associated with human obesity. As sympathetic stimulation triggers energy-consuming processes in adipose tissue, an impaired adipose-neuronal crosstalk is likely to contribute to the disrupted metabolic homeostasis characterising obesity.