In This Issue of Diabetes

Brown adipose tissue (BAT) may have untapped therapeutic potential for treating metabolic disorders including type 2 diabetes and obesity because it not only dissipates energy through the expression of uncoupling protein 1 (Ucp1), but it also plays a role in diet and nonshivering thermogenesis. BAT can emerge from white fat in a process called “browning,” but how this process occurs has remained elusive. In this issue of Diabetes, Carrière et al. (p. 3253) investigate the role of lactate in the browning process and show that this metabolic intermediate—once considered only a glycolytic waste product—may be a critical player in the browning of BAT. In the newly published work, the investigators took on the question of whether lactate contributes to browning via the expression of functional Ucp1. Their experiments demonstrated that lactate enhanced thermogenic Ucp1 expression in murine and human adipose cells, with no parallel increase in expression of Ucp2. In vitro imaging suggested that lactate-induced browning resulted from new UCP1-positive cells as well as activation of preexisting low UCP1 cells. The results also showed that lactate-induced browning requires active peroxisome proliferator–activated receptor γ signaling. To extend these fi ndings in vivo, mice were treated with daily intraperitoneal lactate injections for 11 days and the resulting impact on Ucp1 was examined. The results showed that lactate alone did not change Ucp1 expression in interscapular BAT (iBAT) fat pads. Treating mice with rosiglitazone also had no signifi cant effect on Ucp1 expression in iBAT. While coinjection of lactate and rosiglitazone still showed no enhancement of Ucp1 in iBAT, the coinjection did result in a signifi cant increase in Ucp1 expression in subcutaneous white adipose cells compared with mice that only received rosiglitazone. Taken together, these results demonstrate that lactate stimulates the browning of white adipose cells in mice and humans via changes in Ucp1 gene expression. — Laura Gehl, PhD