Elucidating the crosstalk between the immune system and brown adipose tissue in humans

Brown adipose tissue (BAT) is a promising therapeutic target to improve cardiometabolic health. However, BAT metabolism is dysfunctional in obesity.

Hence, it is highly relevant to ascertain which mechanisms modulate BAT function and how it can be improved in this context.Mice studies indicate that the immune cells-brown adipocytes molecular interactions within BAT modulate its function. Indeed, mice knockout for the transcript Mecp2 in BAT macrophages show impaired BAT function and develop obesity.

Further, cold acclimation activates specific subsets of infiltrated immune cells which improves BAT function.

Altogether points to infiltrated immune cells as key players regulating BAT- but their identity and role, and if they can be targeted to activate BAT in humans, is unknown.The main questions we aim to tackle are: i) Which are the immune cell populations within human BAT? ii) Does local inflammation exist in BAT of obese subjects?

Is it related to their disrupted BAT oxidative and metabolic capacity? iii) Is the BAT oxidative and metabolic capacity improvement, after a 3-month cold acclimation, driven by changes in BAT immune cell profile?

To answer these questions, IMMUNOBAT will characterize the immune cell profile of BAT in lean and obese subjects, using novel single-cell omics in samples obtained by neck surgery.

BAT oxidative and metabolic capacity will be assessed in vivo by state-of-art methods, combining the use of 15O-O2 and 15O-H2O - PET measures with in vitro mitochondrial respiration assays of brown adipocytes.

These measures will be repeated in obese subjects after a 3-month cold acclimation (the most powerful stimulus to activate BAT).IMMUNOBAT will provide new mechanistic insights into obesity pathogenesis, at the same time that it expects to find new tools to improve cardiometabolic health by activating BAT.

Further, it will promote the fellow´s training in adipose biology and immunology, and his growth as an independent and mature researcher