Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - aCROBAT (Circadian Regulation Of Brown Adipose Thermogenesis)

Teaser

The healthcare burden posed by the obesity and diabetes pandemics is rapidly approaching a crippling point and clinical intervention strategies are desperately needed. Brown fat possess a remarkable energy-dissipating and glucose-consuming capacity, yet strategies to exploit...

Summary

The healthcare burden posed by the obesity and diabetes pandemics is rapidly approaching a crippling point and clinical intervention strategies are desperately needed. Brown fat possess a remarkable energy-dissipating and glucose-consuming capacity, yet strategies to exploit their anti-diabetes and anti-obesity therapeutic potential have remained elusive. The chief obstacle has been devising translational methods that can stimulate a maximal, sustained potency of brown fat with limited deleterious side effects.

Brown fat is controlled by both environmental temperature and the body’s clock. Our goal in aCROBAT is to discover and characterize novel factors within these well-conserved programs through which we can unlock the calorie-burning, glucose-consuming power of brown fat. We are currently investigating both cell surface receptors and intracellular enzymes that we identify from unbiased big-datasets.

Work performed

During this reporting period, we have generated unbiased proteomic and transcriptional profiles for our discovery platform to identify key enzymes and receptors controlling brown fat activity. We have validated some of our top hits in fat cells and have made, or are in the process of making, mouse models to study the physiological function of these candidates. Our initial pipeline exceeded expectations and we are currently composing manuscripts on two key enzymes in circadian and cold control of brown adipose metabolism. Furthermore, our study of receptors has progressed so rapidly that we are currently pursuing intellectual property protection and moving towards company spin-off for an obesity drug.

Final results

If we are successful in identifying one or more bona fide drug targets from the cell surface or within, than we anticipate an enormous socio-economic impact. There is a massive demand for potent anti-obesity and anti-diabetes drugs as the number of affected individuals sky-rockets higher and higher. My goal is that by the end of aCROBAT we will have a pipeline of at least 3 viable candidates targeting different aspects of brown fat calorie-burning and glucose consuming functions. Thanks to the critical ERC Starting grant funding, we already have 1 that has passed proof-of-concept.

We also hope that our work will broaden the understanding of how environmental cues like temperature and light interact with the body’s molecular clock to control metabolism and maintain energy balance.