[초청강연] Understanding Fuel Utilization of Brown Adipose Tissue and its Regulation by Nutrient Sensing Pathways
일시: 2021-06-11 11:00 ~ 13:00
발표자: Su Myung Jung, Ph.D. (Sungkyunkwan University)
Brown adipose tissue’s (BAT, also known as Brown Fat) ability to metabolize large quantities of diverse nutrients and dissipate the stored energy as heat (by UCP1) has made it an attractive therapeutic target against obesity including T2D. In particular, active BAT can take up exceptional amounts glucose, which is the basis for detecting BAT in adult humans by 18FDG- PET/CT scanning. However, the exact usage of glucose in active BAT in vivo is unclear. Here, using transcriptomics, metabolomics and stable isotope tracing in mice, we comprehensively elucidated glucose utilization in BAT. While glucose has long-been thought of as a major energy source for thermogenesis (i.e. through glycolysis and TCA) our data suggests glucose supplies many cellular anabolic pathways (synthesis of fatty acids, phospholipids and nucleotides) that support BAT function. We are additionally studying the signaling mechanisms that control brown fat glucose utilization, including the mTORC2 pathway. We recently reported that conditionally deleting the essential mTORC2 subunit Rictor in BAT reprograms metabolism to promote lipid uptake, lipolysis, and thermogenesis at the expense of glucose utilization. Interestingly, mice lacking Rictor only in BAT are protected against obesity and hepatic steatosis reflecting the strong influence BAT can have over systemic metabolic homeostasis. Unexpectedly, mTORC2 loss triggers lipid catabolism, not by impairing classic mTORC2-AKT signaling, but by promoting SIRT6-dependent FoxO1 deacetylation independently of AKT. I will present these findings and discuss our ongoing efforts to explore the fate, functions, and factors that control nutrient utilization in BAT.