Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin.
Title | Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Butiaeva LI, Slutzki T, Swick HE, Bourguignon C, Robins SC, Liu X, Storch K-F, Kokoeva MV |
Journal | Cell Metab |
Volume | 33 |
Issue | 7 |
Pagination | 1433-1448.e5 |
Date Published | 2021 07 06 |
ISSN | 1932-7420 |
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. |
DOI | 10.1016/j.cmet.2021.05.017 |
Alternate Journal | Cell Metab |
PubMed ID | 34129812 |
Grant List | PJT-148790 / / CIHR / Canada PJT-148914 / / CIHR / Canada |