Sanchez Gurmaches Lab
AKT Signaling and ChREBP Transcriptional Activity and Brown Fat

Dissecting the Functional Relationship Between AKT Signaling and ChREBP Transcriptional Activity with Brown Fat Thermogenic Capacity

We have recently identified a key metabolic pathway that regulate and drive the activation of thermogenically competent brown fat in mice and humans. Through whole genome expression profiling, metabolomics, biochemical, physiological and cell biology approaches, we surprisingly found that de novo lipogenesis is the most up-regulated metabolic pathway during BAT activation. Mechanistically, this process requires AKT signaling through a process that seems to require the activity of the transcription factor ChREBP.

Now we are studying the signaling and transcriptional mechanisms associated to this phenomenon in brown and white fats by using tissue specific genetically modified mice and cell lines.

Figure 3.

In our paper in Cell Metabolism in 2018 we revealed a mechanism by which AKT signaling, and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans. Adapted from PMID 29153407.