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, Manuel Mayr*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number7269
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

Fingerprint

Dive into the research topics of 'Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity'. Together they form a unique fingerprint.

Cite this