Novel nuances of human brown fat

There is a current debate in the literature on whether human fat derived from the supraclavicular region should be classified as brown, or as the white fat-derived less potent, brite/beige. This commentary addresses whether the existing classification defined in mice is sufficient to describe the types of thermogenic adipocytes in humans. We recently published a contradictory mRNA expression signature of human supraclavicular fat defined by an upregulation of the brite marker TBX1 along with the classical brown markers ZIC1 and LHX8, as well as genes indicating brown fat activity including UCP1, PGC-1α, and PRDM16; and, finally, a downregulation of the white/brite markers HOXC8 and HOXC9. Subcutaneous fat was used as reference material. Another recent study presents a higher expression of ZIC1 and a lower expression of TBX1 in interscapular compared with supraclavicular fat. Here, however, there was no difference in UCP1, PGC-1α, PRDM16, suggesting both depots had equal brown fat potency. Taken together, supraclavicular brown fat derived from adult humans seems to represent a type of brown fat with distinct features from both subcutaneous white/brite and interscapular brown fat. Therefore, the classification of adipocyte subtypes defined in mice may need reconsideration when applying to humans.