Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity

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 and Manuel Mayr ()
Additional contact information
Elisa Duregotti: School of Cardiovascular Medicine and Sciences
Christina M. Reumiller: School of Cardiovascular Medicine and Sciences
Ursula Mayr: School of Cardiovascular Medicine and Sciences
Maria Hasman: School of Cardiovascular Medicine and Sciences
Lukas E. Schmidt: School of Cardiovascular Medicine and Sciences
Sean A. Burnap: School of Cardiovascular Medicine and Sciences
Konstantinos Theofilatos: School of Cardiovascular Medicine and Sciences
Javier Barallobre-Barreiro: School of Cardiovascular Medicine and Sciences
Arne Beran: University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf
Maria Grandoch: University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf
Alessandro Viviano: University of London
Marjan Jahangiri: University of London
Manuel Mayr: School of Cardiovascular Medicine and Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34846-w

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