Role of SIK3 in energy homeostasis

In the last decades, obesity has become a growing health burden hence the importance of understanding its pathophysiology and the need to search for new therapeutic targets.

Yanagisawa/Funato Lab (Y/F Lab) has recently discover that a splicing mutation in the Salt-inducible kinase 3 (Sik3) gene is involved in determining sleep need , and as well in a likely defective energy homeostasis since mice mutant for exon 13 of the Sik3 gene present an obese phenotype.

The main objective of my proposed action is to identify the role of SIK3 in the central nervous system (CNS) in the regulation of energy balance and study its suitability as a target to develop an anti-obesity therapy.

To achieve this, I will use virogenetic approaches in Sik3-ex13 flox mice and a neuron-specific mutant mice line for exon 13 of Sik3 gene will be generated.

The molecular characterization of the animal models will be conducted by using several cutting-edge techniques such as RNA-Seq and phosphoproteomics. The identified targets will be functionally analyzed using genetics approaches.

In sum, by doing the proposed project I will expect to uncover the influence of a potential new sensor in metabolic homeostasis.

Moreover, this work in combination with the one going already on in Y/F Lab in relation to sleep may allow to understand the interrelationship between sleep disorders and obesity.