PhD: Magalie Haissaguerre

Study of the interaction between Reactive Oxygen Species (ROS) and the mTORC1 pathway in the hypothalamic regulation of energy balance.

Defended on Decembre 15, 2015

Sous la direction du Pr Antoine Tabarin.  Magalie Haissaguerre est doctorante (MD, PhD) au NeuroCentre Magendie INSERM U862 Equipe Dr Daniela COTA Groupe “Physiopathologie de l’équilibre énergétique et obésité”

Doctorante ayant bénéficié d’une bourse MD/PhD LabEx BRAIN.

Study of the interaction between Reactive Oxygen Species (ROS) and the mTORC1 pathway in the hypothalamic regulation of energy balance.

The mechanistic target of rapamycin complex 1 (mTORC1) pathway is an important hypothalamic integrator of nutrients and hormones. Nutrient availability also affects the reactive oxygen species (ROS) in propiomelanocortin (POMC) neurons and regulates neuronal activity. We hypothesize that modulation of mTORC1 activity mediates ROS effects on food intake.

To this purpose, C57Bl6J mice or WT mice and their KO littermates either deficient for the mTORC1 downstream target S6K1 or for the mTORC1 component raptor specifically in POMC neurons (POMC-raptor-KO) were treated with an intracerebroventricular (ICV) injection of the ROS producer H2O2 or the ROS scavenger honokiol, alone or in combination with the mTOR inhibitor rapamycin or the mTOR activator leptin. ICV H2O2 induced phosphorylation of S6K1 within the hypothalamus, increased expression of c-fos, a marker of neuronal activity, in the arcuate nucleus and increased ROS in POMC neurons. These effects were associated with a significant decrease in food intake. The anorexigenic effect of ICV H2O2 was not seen in S6K1-KO mice, in C57Bl6J mice co-treated with rapamycin (an mTOR inhibitor) and in POMC-raptor-KO mice.

Similarly, ICV honokiol administration combined with a leptin injection blunted the anorexigenic effect of leptin, suggesting that leptin requires ROS formation to reduce FI. ICV administration of leptin increased ROS in POMC neurons in C57Bl6J and POMC-raptor-WT mice, but not in POMC-raptor-KO mice. Our results demonstrate that ROS modulators require a functional mTORC1 pathway to regulate food intake and that leptin needs an mTORC1-dependent increase in ROS levels in POMC neurons to decrease food intake.

Keywords : Hypothalamus ; Reactive Oxygen Species ; Mammalian target of rapamycin complex 1; Leptin ; Food intake

 

 

Publications

Haissaguerre M., Courel M., Caron P., Denost S., Dubessy C., Gosse P., Apavouppoulle V., Belleannée G., Jullié M-L., Montero-Hadjadje M., Yon L., Corcuff J-B., Fagour C., Mazerolles C., Wagner T., Nunes M-L., Anouar Y. & Tabarin A. Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular and molecular characteristics. The Journal of Clinical Endocrinology & Metabolism 2013; 98(11) :4346-54.

Haissaguerre M, Tabarin A. Les musts de l’Endocrine « Génétique des tumeurs surrénaliennes ». Annales d’Endocrinologie. 2014

Haissaguerre M, Saucisse N, Cota D. Influence of mTOR in energy and metabolic homeostasis. Molecular and Cellular Endocrinology 2014

Lafond M, Fagour C, Haissaguerre M, Darancette G; Wagner T, Rault A, Tabarin A. Hemodynamic Instability during surgical resection of normotensive incidentally discovered pheochromocytomas. Journal of Clinical Endocrinology & Metabolism 2014

Bermudez-Silva FJ, Romero-Zerbo SY, Haissaguerre M, Ruz-Maldonado I, Tabarin A, Marsicano G, Cota D. Cannabinoid CB1 receptors and mTORC1 signalling pathway interact to modulate glucose homeostasis. Accepté à Disease Models & Mechanisms 2015

ARTICLES SOUMIS OU EN PREPARATION

Haissaguerre M, Leboulleux S, Bonichon F, Borget I, Chougnet C, Al Ghuzlan A, Hartl D, Mirghani H, Deandreis D, Baudin E, Schlumberger M. Impact of molecular targeted therapies in patients with bone metastases of differentiated thyroid carcinoma. Article en préparation

Haissaguerre M, Ferriere A, Clark S, Guzman-Quevedo P, Tabarin A, Cota D. The potent role of mTORC1 in the modulation of food intake induced by the hypothalamic reactive oxygen species. Article en cours de soumission à Journal of Neuroscience

Velayoudom-Cephise F-L, Haissaguerre M, Tabarin A. Etiopathogeny of primary adrenal hypercortisolism. Article en cours de soumission à Frontiers in Endocrinology


Jury

  • Mme. LAYE Sophie
    Université de Bordeaux
    Président
  • Mme. LELOUP Corinne
    Université de Dijon
    Rapporteur
  • Mme. BOUSQUET Corinne
    Université de Toulouse
    Rapporteur
  • Mme GUIBERT Christelle
    Université de Bordeaux
    Examinateur
  • Mme COTA Daniela
    Université de Bordeaux
    Examinateur
  • M. TABARIN Antoine
    Université de Bordeaux
    Directeur de thèse

Directeur de thèse

Antoine Tabarin
Professeur – PhD

UFR Sciences médicales
CHU de Bordeaux 
Enseignant Chercheur
Neurocentre Magendie
INSERM U862
Physiopathologie de la plasticité neuronale
dans l’équipe: Physiopathologie de l’équilibre énergétique et obésité de Daniela Cota

Publications d’Antoine Tabarin

Last update: 6 April 2018