Adaptive thermogenesis in white adipose tissue: is lactate the new brown(ing)?

Abstract

The prevalence of obesity and type 2 diabetes has become a major economic and medical burden worldwide. Increased food intake and reduced physical activity have contributed to a shift in energy balance, resulting in excess energy storage in the white adipose tissue (WAT) depots. In contrast to WAT, brown adipose tissue (BAT) converts excess energy into heat via uncoupled respiration, which is dependent, in part, on expression by brown adipocytes of the uncoupling protein 1 (UCP1). Thus, an attractive strategy to reduce energy storage is to increase the levels of brown adipocyte activity. Although WAT does not normally express UCP1 or exhibit uncoupled respiration, WAT depots are capable of great plasticity. In response to cold exposure or genetic modifications, mouse white adipocytes can be induced to exhibit brown adipocyte–like character. These cells are known as “brite” (for brown-in-white) or “beige” adipocytes. Factors that are known to increase “browning” in mouse WAT include the transcription factors PGC1α, PRDM16, and members of the PPAR family (1). Additionally, treatment with metabolites, such as bile acids, prostaglandins, and retinoids, promotes the browning of WAT (2). Beige adipocytes express UCP1 and accumulate multilocular lipid droplets similar to genuine brown adipocytes but exhibit a gene expression signature that is distinct from classic brown adipocytes (3,4 …