Molecular signatures and functional analysis of beige adipocytes induced from in vivo intra-abdominal adipocytes.

ABSTRACT

Beige adipocytes can be induced from white adipocytes and precursors upon stimulation by cold temperatures and act like brown adipocytes to increase energy expenditure. Most in vivo studies examining the mechanisms for the induction of beige adipocytes have focused on subcutaneous white adipose tissue (sWAT; benign fat) in the mouse. How intra-abdominal WAT (aWAT; malignant fat) develops into beige adipocytes remains obscure, largely because there is a lack of a good animal model for the induction of beige adipocytes from aWAT. To better understand the development of beige adipocytes from mammalian WATs, especially aWAT, we induced beige adipocytes from bat aWAT and mouse sWAT by exposure to cold temperatures and analyzed their molecular signatures. RNA sequencing followed by whole genome-wide expression analysis shows that beige adipocytes induced from bat aWAT, rather than sWAT, have molecular signatures resembling those of mouse sWAT-induced beige adipocytes and exhibit dynamic profiles similar to those of classical brown adipocytes. In addition, we identified molecular markers that were highly enriched in beige adipocytes and conserved between bat aWAT and mouse sWAT, a set that included the genes Uqcrc1 and Letm1. Furthermore, knockdown of Uqcrc1 and Letm1 expression shows that they are required not only for beige adipocyte differentiation but also for preadipocyte maturation. This study presents a new model for research into the induction of beige adipocytes from aWAT in vivo, which, when combined with models where beige adipocytes are induced from sWAT, provides insight into therapeutic approaches for combating obesity-related diseases in humans.