Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin.

TitleLeptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin.
Publication TypeJournal Article
Year of Publication2021
AuthorsButiaeva LI, Slutzki T, Swick HE, Bourguignon C, Robins SC, Liu X, Storch K-F, Kokoeva MV
JournalCell Metab
Volume33
Issue7
Pagination1433-1448.e5
Date Published2021 07 06
ISSN1932-7420
Abstract

Knowledge of how leptin receptor (LepR) neurons of the mediobasal hypothalamus (MBH) access circulating leptin is still rudimentary. Employing intravital microscopy, we found that almost half of the blood-vessel-enwrapping pericytes in the MBH express LepR. Selective disruption of pericytic LepR led to increased food intake, increased fat mass, and loss of leptin-dependent signaling in nearby LepR neurons. When delivered intravenously, fluorescently tagged leptin accumulated at hypothalamic LepR pericytes, which was attenuated upon pericyte-specific LepR loss. Because a paracellular tracer was also preferentially retained at LepR pericytes, we pharmacologically targeted regulators of inter-endothelial junction tightness and found that they affect LepR neuronal signaling and food intake. Optical imaging in MBH slices revealed a long-lasting, tonic calcium increase in LepR pericytes in response to leptin, suggesting pericytic contraction and vessel constriction. Together, our data indicate that LepR pericytes facilitate localized, paracellular blood-brain barrier leaks, enabling MBH LepR neurons to access circulating leptin.

DOI10.1016/j.cmet.2021.05.017
Alternate JournalCell Metab
PubMed ID34129812
Grant ListPJT-148790 / / CIHR / Canada
PJT-148914 / / CIHR / Canada