Responsable : Mohammed Taouis
NMPA étudie les mécanismes impliqués dans l’installation de la leptino- et insulino-résistances au niveau hypothalamique. Notre objectif est l’étude de l’influence à long terme de l’environnement périnatal (endocrinien et métabolique) sur le contrôle hypothalamique de l’homéostasie énergétique.
1. Molecular and cellular mechanisms involved in hypothalamic insulin and leptin resistance
As previously described, hypothalamic leptin sensitivity is critical in the control of energy homeostasis and neuronal organization. Previously, we have demonstrated that leptin, insulin, CNTF and serotonin share common signaling pathways. We have showed that both leptin and insulin resistances are associated, linking then obesity to type 2 diabetes through most likely resistin. This part of our project will be organized in the following tasks.
Cellular and molecular mechanisms of resistin/TLR4-dependent hypothalamic nuclei inflammation and insulin resistance
Resistin induces hypothalamic neuro-inflammation (Benomar et al., 2013)
2. Impact of hypothalamic hormonal and metabolic environment during perinatal periods
* Expression profile of hypothalamic microRNA :
According to our previous studies we hypothesize that changes of specific miRNA expression levels may be involved, at least partially, in the process of diet or hormonal induced alteration of hypothalamic neuronal organization during early life. Furthermore, we will continue the improvement this technique by developing a guideline to quantify barcoding impact in multiplex microRNA expression profiles using Illumina technology.
Validation and the physiological relevance of miRNAs.
The characterization of specific miRNAs will be validated by in situ hybridization (ISH) to specifically confirm their localization in specific hypothalamic nuclei.
Validation and the physiological relevance of hypothalamic miRNAs