Distinct transcriptomes of dormant and active brown fat within the perirenal depot of adult humans

We here define a novel concept of dormant brown fat in adult humans present in most of the perirenal fat depot. This was contrasted by an active brown fat phenotype accumulating near the adrenal gland. Transcriptomics analysis of active and dormant brown fat and subcutaneous white fat revealed a clear separation. We identified SPARC as a candidate adipokine and ZNF703, a transcriptional regulator, both potentially sustaining BAT in a dormant state in the absence of sympathetic activation. Brown fat precursor cells were present in the entire perirenal fat depot, regardless of state. When differentiated in vitro, these cells responded to acute norepinephrine stimulation by increasing UCP1 gene expression and uncoupled respiration, confirming a brown fat phenotype. Our findings suggest a current underestimation of brown fat abundance in adult humans and provide basis for future research in re-activating dormant brown fat as a strategy to combat obesity and metabolic disease.