Regulation of beige adipocyte plasticity in inguinal white adipose tissue.

ABSTRACT Beige adipocyte plasticity refers to the ability to transform between thermogenic active and inactive states in accordance to environment fluctuations. For example, cold induces the formation of beige adipocytes, while warm temperature and nutrient excess lead to their disappearance. Previously, we have described the beige adipocyte renaissance phenomenon that the white adipocytes to be converted to beige adipocytes by cold indeed have Ucp1 expression history (being Ucp1+-lineage). Interestingly, beige adipocyte renaissance is regulated by Ucp1--lineage white adipocytes non-cell autonomously. This proposal will further delineate the cellular and molecular mechanisms of beige adipocyte plasticity. Aim 1 will investigate the in vivo relevance of HDAC4:PRDM16 complex in Ucp1--lineage white adipocytes that is relevant to beige adipocyte plasticity. Aim 2 will determine the regulatory mechanisms of HDAC4:PRDM16 complex-dependent gene network at molecular and chromatin levels. Aim 3 will exploit the potential contribution of extracellular matrix remodeling to the maintenance of Ucp1+-lineage beige adipocytes. Prior researches have suggested a correlation between activities of beige adipocytes and metabolic fitness in both rodents and humans. Investigations in this direction may provide novel druggable targets to treat obesity and related metabolic disorders.