How brown is brown fat that we can see?

There are many unanswered questions related to the heterogeneity of adipose tissue depots and the paucity of their function, development, and organization at the cellular level. Much effort has been directed at studying white adipose tissue (WAT), the driver of obesity and the associated metabolic disease. In recent years, the importance of brown adipose tissue (BAT) has also been appreciated. While BAT depots are prominent in many small mammal species, their detection in adult humans has been technically challenging and the identity of brown human adipocytes found within depots of WAT has remained controversial. We recently reported a peptide probe that binds to BAT vasculature and, when coupled with a near-infrared fluorophore, can be used to detect BAT in whole body imaging. This probe reliably discriminates between endothelium associated with brown or brown-like (beige/brite) adipocytes and endothelium of visceral WAT. Improved probes based on this approach could aid in assessing human adipose tissue body distribution and remodeling, which is a process underlying various pathologies. This commentary aims at discussing open questions that need to be addressed before full clinical advantage can be taken from adipose tissue imaging, as well as its metabolic activation strategies.