Establishing the significance of brite/beige versus classical brown adipocytes in the control of energy expenditure and glucose metabolism

Thermogenesis-competent adipocytes – classical brown and brite/beige – possess the ability to increase energy expenditure and are therefore envisaged as promising therapeutic targets in the fight against obesity.

However, in humans, and in mice maintained under human-relevant conditions (thermoneutrality, an energy-rich diet and middle-age), these thermogenic adipocytes are present in very low amounts.

It is the goal of the project to: a) explore possibilities to recruit large quantities of these energy-dissipating adipocytes, and b) establish the relative significance of the two thermogenesis-competent adipose cell types for energy expenditure and glucose metabolism under human-relevant conditions.

We will create transgenic mouse models for loss- and gain-of-thermogenic function selectively for the two types of thermogenic adipocytes and conduct metabolic phenotyping – energy metabolism, thermogenic competence and glucose and lipid metabolism – to identify the quantitative importance of the two types of adipocytes.

Demonstration of a possibility to recruit large quantities of energy-dissipating and metabolically beneficial brown and brite/beige adipocytes in mice maintained under human-relevant conditions would strongly suggest that humans possess a similar potential for thermogenic recruitment, implying that humans also have the ability to increase energy expenditure, restrict the development of obesity and diminish obesity-driven comorbidities, notably type 2 diabetes.