Journal Article

DKFZ-2026-01782

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The perineurium integrates leptin with its sympathetic outflow to protect against obesity.

Sarker, G. ; Haberman, E. ; Chandran, A. ; Monfeuga, T. ; Maroteau, C. ; Lundh, S. ; Oliveira, D. S. ; Raimondi, A. ; Ziegler, K. ; Gomes, T. ; Cordeiro, T. N. ; Parekh, K. ; Schmid, E. ; Fernández-Sanmartín, P. ; Griebel, A. ; Martinez-Sanchez, N. ; Arus, B.DKFZ* ; Cheung, S. W. ; Zhu, Y. ; Shaked, M. ; Knowles, S. C. L. ; Engelhardt, S. H. ; Iannacone, M. ; Scherer, P. E. ; López, M. ; Toledo, E. M. ; Domingos, A.

2026
Springer Nature [London]

Abstract: The regulatory mechanism of leptin's afferent action in the brain is contingent upon the efferent sympathetic innervation of white and brown adipose tissues. Nonetheless, the peripheral regulation governing the afferent-efferent balance remains ambiguous. Here we show the enriched expression of both leptin receptor (Lepr) and β2-adrenergic receptor (Adrb2) in perineurial cells that form a barrier around sympathetic ganglia and nerve bundles in adipose tissues, using single-cell RNA sequencing on mouse sympathetic ganglia. Lepr+ sympathetic perineurial cells (SPCs) are molecularly similar to endothelial cells. Conditional knockout of Adrb2 in Lepr+ cells, including SPCs, predisposes male mice to obesity by lowering energy expenditure and thermogenesis without affecting food intake. Notably, obesity-associated hyperleptinaemia causes apoptosis in SPCs, disrupting the perineurial barrier and concomitant adipose sympathetic neuropathy. This deleterious effect can be reversed by partial reduction of leptin or sympathomimetic β2-adrenergic receptor agonism. Clinically, we observed a male-specific synergistic effect of LEPR and ADRB2 polymorphisms on increased body mass index risk in a large European population. We propose that SPCs coordinate the afferent and efferent arms of the neuroendocrine loop of leptin action to regulate energy expenditure and body weight.

Note: #NCTZFB26# / 2026 Jul;8(7):1563-1582

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Contributing Institute(s):

1. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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