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Leptin brain entry via a tanycytic LepR–EGFR shuttle controls lipid metabolism and pancreas function
- Source :
- Nature Metabolism, Nature Metabolism, Nature Publishing Group, 2021, 3 (8), pp.1071-1090. ⟨10.1038/s42255-021-00432-5⟩, Nature metabolism
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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 and lipogenesis but also glucose intolerance through attenuated insulin secretion by pancreatic β-cells, possibly via altered sympathetic nervous tone. Tanycytic LepRb–EGFR-mediated transport of leptin could thus be crucial to the pathophysiology of diabetes in addition to obesity, with therapeutic implications. Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.
- Subjects :
- Leptin
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Ependymoglial Cells
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Neuroendocrinology
Biology
Article
03 medical and health sciences
0302 clinical medicine
Insulin-Secreting Cells
Physiology (medical)
Internal medicine
Receptors
Diabetes Mellitus
Internal Medicine
medicine
Phosphorylation
Receptor
Pancreas
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Leptin receptor
Tanycyte
digestive, oral, and skin physiology
Brain
Cell Biology
Lipid Metabolism
Energy Metabolism
ErbB Receptors
Receptors, Leptin
Endocrinology
medicine.anatomical_structure
Hypothalamus
Lipogenesis
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Hormone
Subjects
Details
- ISSN :
- 25225812
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Nature Metabolism
- Accession number :
- edsair.doi.dedup.....a86b0ea128dc61aa3701d4f716eb37ac