Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions

被引：71

作者：

Imbernon, Monica ^{[1
]}

Saponaro, Chiara ^{[2
]}

Helms, Hans Christian Cederberg ^{[1
,3
]}

Duquenne, Manon ^{[1
]}

Fernandois, Daniela ^{[1
]}

Deligia, Eleonora ^{[1
]}

Denis, Raphael G. P. ^{[4
]}

Chao, Daniela Herrera Moro ^{[4
]}

Rasika, Sowmyalakshmi ^{[1
]}

Staels, Bart ^{[5
]}

Pattou, Francois ^{[2
]}

Pfrieger, Frank W. ^{[6
]}

Brodin, Birger ^{[3
]}

Luquet, Serge ^{[4
]}

Bonner, Caroline ^{[2
]}

Prevot, Vincent ^{[1
]}

机构：

[1] Univ Lille, Lille Neurosci & Cognit, INSERM,Lab Dev & Plast Neuroendocrine Brain, CHU Lille,UMR S 1172,European Genom Inst Diabet E, F-59000 Lille, France

[2] Univ Lille, Inst Pasteur Lille, EGID, Inserm U1190,CHU Lille, F-59000 Lille, France

[3] Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark

[4] Univ Paris, CNRS, BFA, UMR 8251, F-75013 Paris, France

[5] Univ Lille, INSERM, CHU Lille, Inst Pasteur Lille,U1011,EGID, Lille, France

[6] Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, Ctr Natl Rech Sci, Strasbourg, France

来源：

CELL METABOLISM | 2022年 / 34卷 / 07期

基金：

欧洲研究理事会;

关键词：

GLUCOSE-HOMEOSTASIS; ARCUATE NUCLEUS; GLP-1; BRAIN; RECEPTOR; ACTIVATION; EXENDIN-4; OXIDATION; RELEASE; LEPTIN;

D O I：

10.1016/j.cmet.2022.06.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 transcyto-sis 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 homeo-stasis.

引用

页码：1054 / +

页数：18

共 48 条

[1] Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor-Expressing Glutamatergic Neurons [J].