Tanycyte/arcuate Neuron communications in the regulation of energy balance

The escalating pandemic of obesity and type-2 diabetes represents one of the most pressing and costly biomedical challenges confronting modern society.

The brain's impaired ability to sense and respond to variations in energy homeostasis is increasingly recognized as playing a role in the pathophysiology of these disorders.

By sensing the nutritional status of the organism, distinct neural cell populations –including neurons and glia present in the arcuate nucleus of the hypothalamus (ARH)– tightly regulate energy balance.

In the last decade, it has become clear that tanycytes –hypothalamic glial cells lining the bottom of the third ventricle and sending a single basal process into the ARH– are also able to detect variations of nutrient and hormone levels.

Henceforth described as “sensors” of the metabolic state, tanycytes would then modulate neuronal function in order to regulate energy balance.

However, the mechanisms underlying the communication between tanycytes and ARH neurons in the context of metabolism remain largely unexamined.The overall objective of this project is to elucidate the molecular, structural and functional organization of tanycyte/ARH neuron communications, and their involvement in the regulation of energy balance.

A multidisciplinary approach including neuroanatomy, molecular biology, and physiology will be implemented to achieve four specific aims: 1)To decipher the genetic and neuroanatomical features of tanycyte/ARH neuron metabolic units2)To ascertain the impact of tanycyte Annexin A1 on ARH neuronal function3)To uncover the role of tanycyte local translation in specific tanycyte/neuron communications4) To reveal the impact of tanycyte glucose-sensing on ARH neuronal gene expressionThe elucidation of tanycyte/neuron communications will be essential to explain the regulation of food intake and to allow the development of new therapeutic strategies for obesity and associated metabolic syndromes.