Regulation of beige adipocyte maintenance and its impact on metabolic outcomes

Title: Regulation of beige adipocyte maintenance and its impact on metabolic outcomes Project Summary/Abstract A potential therapeutic target to curb the global obesity and diabetes epidemic is thermogenic beige fat within white adipose tissue (WAT). Unlike white adipocyte which stores fat, beige adipocytes are stimulated thermogenic fat cells in WAT that robustly consume lipid and glucose. However, Beige adipocytes quickly disappear upon the removal of stimuli, a process further accelerated by age and obesity. This creates a key challenge to explore beige adipocytes as a sustainable therapy for chronic metabolic diseases. A long-term goal of my laboratory is to understand the development and maintenance of beige adipocytes, and the metabolic outcomes. In our preliminary studies using unique mouse models, we demonstrate that beige adipocytes can be induced and maintained by pharmacological and genetical measures. Further, our preliminary results suggest that these induced beige adipocytes are maintained in the older mice, even without continuous stimulation. These exciting findings, although preliminary in nature, suggest novel measures to use beige adipocyte as potential therapeutics to treat obesity, diabetes, and other metabolic diseases. In this application, we will investigate whether the sustained beige adipocytes can improve the metabolic fitness under both health and disease conditions, thereby achieving anti-obesity and anti-diabetes effects. Furthermore, we will elucidate the critical molecular mechanisms by which beige adipocyte identity is preserved. In addition, we will employ cell- type selective transcriptomic approach to comprehensively characterize the molecular components involved in beige adipocyte maintenance.