Human brown fat may actually be beige

By Eleanor McDermid

Beige fat cells are more closely related to white than brown fat cells, say researchers who found that brown fat deposits in humans appear to be composed of beige cells.

The team's experiments in mice show that although "beige" cells have similar thermogenic capacity to brown cells, they actually arise from adipocyte precursor cells, rather than from a muscle-cell lineage as brown cells do.

In their basal state, similar to white cells, beige cells expressed very low levels of genes involved in thermogenesis, including mitochondrial Ucp1, the researchers report in Cell.

But on stimulation with cyclic adenosine monophosphate ‑ cAMP ‑ levels of Ucp1 messenger RNA in the beige cells increased to become on a par with levels in stimulated brown fat cells. Because basal levels were so much lower in beige relative to brown cells, this represented a very large increase ‑ about 150-fold compared with 40-fold on stimulation of brown cells.

Mitochondrial respiration, which is crucial for adaptive thermogenesis, increased twofold in stimulated beige cells in vivo, 1.2-fold in brown cells, and barely changed in white cells.

"Thus, the beige cells have the capability to switch between an energy storage and energy dissipation phenotype in a manner that other fat cells lack," say Bruce Spiegelman (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues.

Beige cells expressed several genes that distinguished them from white and brown cells. One of these genes encoded a cell surface marker, CD137, which also identified beige precursor cells.

Spiegelman et al previously identified a protein ‑ irisin ‑ that provokes the "browning" of white adipocytes. Treating the beige precursor cells with irisin caused them to differentiate into cells expressing many genes associated with brown cells, whereas no such effect was seen for white fat precursor cells. This suggests that the group's previous findings were explained by the existence of beige cells.

Finding these cell-specific markers also allowed the researchers to study beige cells in humans. They found that cells from brown fat biopsies ‑ identified by their increased expression of UCP1 relative to that in white fat biopsies ‑ had a gene expression profile characteristic of beige cells in mice. They also had the typical beige cell surface markers, including CD137.

"If these UCP1-positive cells are functionally similar to the rodent beige cells, this might explain why a relatively low proportion of humans show [positron emission tomography]-positive fat deposits until activated with a brief cold exposure," concludes the team.

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