Title :

Preclinical assessment of leptin transport into the cerebrospinal fluid in diet-induced obese minipigs

Author(s) :

Chmielewski, Alexandra [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Hubert, Thomas [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète (RTD) - U1190
Descamps, Amandine [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Mazur, Danièle [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Daoudi, Mehdi [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Ciofi, Philippe [Auteur]
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]
Fontaine, Christian [Auteur]
Université de Lille
Caiazzo, Robert [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète (RTD) - U1190
Pattou, Francois [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète (RTD) - U1190
Prevot, Vincent [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Pigeyre, Marie [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Recherche translationnelle sur le diabète - U 1190 [RTD]

Journal title :

Obesity (Silver Spring, Md.)

Abbreviated title :

Obesity (Silver Spring)

Volume number :

27

Pages :

950-956

Publication date :

2019-04-21

ISSN :

1930-739X

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Objective A minipig model was employed to explore the changes in endogenous leptin transport into the central nervous system and in hypothalamic sensitivity to exogenous leptin when individuals are placed on high-fat ...
Show more >Objective A minipig model was employed to explore the changes in endogenous leptin transport into the central nervous system and in hypothalamic sensitivity to exogenous leptin when individuals are placed on high-fat diet (HFD) compared with standard diet. Methods Serum and cerebrospinal fluid (CSF) leptin concentrations during 10 weeks of HFD versus standard diet and exogenous leptin-induced STAT3 phosphorylation in the hypothalamus of minipigs were assessed, and the hypothalamic leptin-sensitive cells were characterized by immunofluorescence. Results The efficiency of the passage of endogenous blood-borne leptin into the CSF (measured as the log [CSF:serum leptin ratio]) decreased over time in minipigs fed a HFD (β = –0.04 ± 0.005 per kilogram of weight gain in HFD; P < 0.0001), while it remained stable in minipigs fed a standard diet. However, the ability of peripherally administered leptin to activate its receptor in hypothalamic neurons was preserved in obese minipigs at 10 weeks of HFD. Conclusions Together, these data are consistent with the existence of an early-onset tranport deficiency for endogenous circulating leptin into the brain in individuals developing obesity, preceding the acquisition of hypothalamic leptin resistance. Although additional studies are required to identify the underlying mechanisms, our study paves the way for the development of new preclinical pharmacological models targeting the restoration of the shuttling of peripheral leptin into the central nervous system to manage obesity.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Recherche translationnelle sur le diabète (RTD) - U1190

Research team(s) :

Développement et plasticité du cerveau neuro-endocrine

Submission date :

2021-06-23T11:43:21Z
2024-03-14T09:23:11Z