Perineurium integrates leptin with its sympathetic outflow to protect against obesity

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.