Obesity, Diabetes and Comorbidities

A) HEALTHY EXPANSION OF WHITE ADIPOSE TISSUE (WAT).

WAT is a critical metabolic organ that contributes to energy storage, endocrine homeostasis and metabolic flexibility by efficiently storing surplus fuel and quickly mobilising lipids/energy to supply peripheral organs. In the context of obesity, we are not asking why obese patients develop comorbidities, but rather how to make them resilient and promote healthy expansion in the face of comorbidities. We hypothesise that this depends on the mechanisms that keep adipose tissue healthy regardless of its size.

To answer this question, we will:

• Identify genetic variants associated with an increased risk of obesity that also have protective cardiometabolic effects, and viceversa.
• Prioritise and genetically mutate candidate genes using adipocyte cellular models.
• Validate the functionality of the candidate genes in vitro and in vivo.

B) BROWN ADIPOSE TISSUE (BAT) RECRUITMENT AND ACTIVATION

Using the same approaches indicated for WAT, we will also identify the molecular mechanisms controlling energy expenditure via sympathetic tone to BAT, as well as directly regulating its activation in both the mouse and human contexts.

C) ENDOCRINE DISRUPTING CHEMICAL (EDC) IMPACT ON MASLD PROGRESSION

We have recently added a new area of interest to our research, namely understanding how the exposome, particularly in the form of EDCs, affects the progression of MASLD, a condition that is often linked to obesity.