Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function.

ABSTRACT: Metabolic health depends on the brain's ability to control food intake and nutrient use versus storage, processes that require peripheral signals such as the adipocyte-derived hormone, leptin, to cross brain barriers and mobilize regulatory circuits. We have previously shown that hypothalamic tanycytes shuttle leptin into the brain to reach target neurons. Here, using multiple complementary models, we show that tanycytes express functional leptin receptor (LepR), respond to leptin by triggering Ca²⁺ waves and target protein phosphorylation, and that their transcytotic transport of leptin requires the activation of a LepR-EGFR complex by leptin and EGF sequentially. Selective deletion of LepR in tanycytes blocks leptin entry into the brain, inducing not only increased food intake

SUBMITTER: Duquenne M 

PROVIDER: S-EPMC7611554 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature