[대학원 생명과학과 세미나 안내]
연사 : 정수명 교수(성균관대학교 생명과학과)
연제 : Brown Fat as a Nutrient Sink and its Therapeutic Potential in Metabolic Disease
일시 : 2022년 05월 20일 (금) 오후 4시 30분
장소 : 대면 및 온라인 화상 강의로 진행됩니다.
초청교수 : 구승회 교수
Abstract
Brown adipose tissue’s (BAT, also known as Brown Fat) ability to metabolize diverse menu of 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 copious amount of 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 unknown. 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 thermogenic fuel (i.e. through glycolysis and TCA), our data suggests glucose feeds into many cellular anabolic pathways (de novo fatty acids, glycerol-lipids and nucleotides) that support BAT functioning. We are additionally studying nutrient-sensing pathways that control brown fat glucose utilization, including mTOR signaling. 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 that 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 may therapeutically stimulate BAT’s nutrient utilization.
Keywords: Brown fat, Brown adipose tissue, Brown adipocyte, Metabolism, mTOR