Cloning of BUG demonstrates the existence of a brown preadipocyte distinct from a white one

Several indirect arguments agree with the existence of a brown preadipocyte distinct from a white one. Nevertheless, to date, no molecular marker has been available to directly in vivo demonstrate this hypothesis.

The aim of this study was to find a gene expressed in brown preadipocyte but not in white and to use it as a molecular marker to analyse brown preadipocyte recruitment in different physiological and physiopathological situations.

Differential display was performed on stromal-vascular and adipocyte fractions of white and brown adipose tissues in rat.

We identified a new gene, BUG, preferentially expressed in the stromal-vascular fraction of brown fat vs other adipose tissues fractions in adult rat. This RNA is also highly expressed in heart and, to a lesser extent, in other tissues such as kidney and brain. The BUG transcript is detected by in situ hybridization in putative preadipocytes within brown adipose tissue. Its level is transiently and specifically up-regulated during early stages of brown preadipocyte differentiation in a primary culture system, before the acquisition of late brown adipocyte phenotype. During development, BUG can be detected before the emergence of UCP-1 expression. In adult rats, BUG expression is inversely associated to brown adipose tissue (BAT) activation during cold exposure as well as in obese animals.

The pattern of BUG expression agrees with an early divergence between brown and white adipocyte lineages. It also reveals the existence of a pool of committed brown preadipocytes within BAT that are recruited during cold exposure. BUG expression is increased in obese animals, suggesting that an early defect in brown preadipocyte differentiation could account for impaired BAT function in genetically obese rats.