Title :

Tanycytic transcytosis inhibition disrupts energy balance, glucose homeostasis and cognitive function in male mice

Author(s) :

Duquenne, Manon [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Excellence Laboratory LabEx DISTALZ
Deligia, Eleonora [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Excellence Laboratory LabEx DISTALZ
Folgueira, Cintia [Auteur]
Universidade de Santiago de Compostela [España] = University of Santiago de Compostela [Spain] = Université de Saint-Jacques-de-Compostelle [Espagne] [USC]
Bourouh, Cyril [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Caron, Emilie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Excellence Laboratory LabEx DISTALZ
Pfrieger, Frank [Auteur]
Institut des Neurosciences Cellulaires et Intégratives [INCI]
Schwaninger, Markus [Auteur]
Universität zu Lübeck = University of Lübeck [Lübeck]
Nogueiras, Ruben [Auteur]
Universidade de Santiago de Compostela [España] = University of Santiago de Compostela [Spain] = Université de Saint-Jacques-de-Compostelle [Espagne] [USC]
Annicotte, Jean-Sébastien [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Université de Lille
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Imbernon, Monica [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Excellence Laboratory LabEx DISTALZ
Prévot, Vincent [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Excellence Laboratory LabEx DISTALZ

Journal title :

Molecular metabolism

Pages :

101996

Publisher :

Elsevier

Publication date :

2024-07

ISSN :

2212-8778

English keyword(s) :

Tanycytes
Bloodebrain barrier
Blood-cerebrospinal fluid barrier
Transports
Hypothalamus
Normal-weight central obesity

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Objectives: In Western society, high-caloric diets rich in fats and sugars have fueled the obesity epidemic and its related disorders. Disruption of the body-brain communication, crucial for maintaining glucose and energy ...
Show more >Objectives: In Western society, high-caloric diets rich in fats and sugars have fueled the obesity epidemic and its related disorders. Disruption of the body-brain communication, crucial for maintaining glucose and energy homeostasis, arises from both obesogenic and genetic factors, leading to metabolic disorders. Here, we investigate the role of hypothalamic tanycyte shuttles between the pituitary portal blood and the third ventricle cerebrospinal fluid in regulating energy balance. Methods: We inhibited vesicle-associated membrane proteins (VAMP1-3)-mediated release in tanycytes by expressing the botulinum neurotoxin type B light chain (BoNT/B) in a Cre-dependent manner in tanycytes. This was achieved by injecting either TAT-Cre in the third ventricle or an AAV1/2 expressing Cre under the control of the tanycyte-specific promoter iodothyronine deiodinase 2 into the lateral ventricle of adult male mice. Results: In male mice fed a standard diet, targeted expression of BoNT/B in adult tanycytes blocks leptin transport into the mediobasal hypothalamus and results in normal-weight central obesity, including increased food intake, abdominal fat deposition, and elevated leptin levels but no marked change in body weight. Furthermore, BoNT/B expression in adult tanycytes promotes fatty acid storage, leading to glucose intolerance and insulin resistance. Notably, these metabolic disturbances occur despite a compensatory increase in insulin secretion, observed both in response to exogenous glucose boluses in vivo and in isolated pancreatic islets. Intriguingly, these metabolic alterations are associated with impaired spatial memory in BoNT/B-expressing mice. Conclusions: These findings underscore the central role of tanycytes in brain-periphery communication and highlight their potential implication in the age-related development of type 2 diabetes and cognitive decline. Our tanycytic BoNT/B mouse model provides a robust platform for studying how these conditions progress over time, from prediabetic states to full-blown metabolic and cognitive disorders, and the mechanistic contribution of tanycytes to their development. The recognition of the impact of tanycytic transcytosis on hormone transport opens new avenues for developing targeted therapies that could address both metabolic disorders and their associated cognitive comorbidities, which often emerge or worsen with advancing age.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL