| First Author | Butiaeva LI | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 7 | Pages | 1433-1448.e5 |
| PubMed ID | 34129812 | Mgi Jnum | J:325183 |
| Mgi Id | MGI:6721367 | Doi | 10.1016/j.cmet.2021.05.017 |
| Citation | Butiaeva LI, et al. (2021) Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin. Cell Metab 33(7):1433-1448.e5 |
| abstractText | 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. |
