Tanycytes Control Hypothalamic Liraglutide Uptake and Its Anti-obesity Actions

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2022 Jun 18

PMID 35716660

Authors

Monica Imbernon

Chiara Saponaro

Hans Christian Cederberg Helms

Manon Duquenne

Daniela Fernandois

Eleonora Deligia

Raphael G P Denis

Daniela Herrera Moro Chao

Sowmyalakshmi Rasika

Bart Staels

Francois Pattou

Frank W Pfrieger

Birger Brodin

Serge Luquet

Caroline Bonner

Vincent Prevot

Affiliations

Soon will be listed here.

Abstract

Liraglutide, an anti-diabetic drug and agonist of the glucagon-like peptide one receptor (GLP1R), has recently been approved to treat obesity in individuals with or without type 2 diabetes. Despite its extensive metabolic benefits, the mechanism and site of action of liraglutide remain unclear. Here, we demonstrate that liraglutide is shuttled to target cells in the mouse hypothalamus by specialized ependymoglial cells called tanycytes, bypassing the blood-brain barrier. Selectively silencing GLP1R in tanycytes or inhibiting tanycytic transcytosis by botulinum neurotoxin expression not only hampers liraglutide transport into the brain and its activation of target hypothalamic neurons, but also blocks its anti-obesity effects on food intake, body weight and fat mass, and fatty acid oxidation. Collectively, these striking data indicate that the liraglutide-induced activation of hypothalamic neurons and its downstream metabolic effects are mediated by its tanycytic transport into the mediobasal hypothalamus, strengthening the notion of tanycytes as key regulators of metabolic homeostasis.

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