Novel signal transduction components regulating brown adipocyte biology

Hovedområde:Cell biology
Målgruppe:Molecular Biomedicine, Biochemistry, Biology

White and brown adipose tissues play pivotal roles in whole-body energy metabolism. White adipose tissue (WAT) is the largest energy reserve in the body, and white adipocytes secrete hormones (adipokines) affecting various key metabolic organs. Excessive accumulation of WAT causes obesity that predisposes to hypertension, diabetes, cardiovascular disease and certain cancers. Brown adipose tissue (BAT) is specialized in energy dissipation by which the resident brown adipocytes upon activation convert energy-rich substrates to heat by uncoupled respiration (thermogenesis). This uncoupled respiration is induced by cold exposure and is dependent on uncoupling protein 1 (UCP1), which is present exclusively in thermogenic adipocytes. Brown adipocytes, like white adipocytes, secrete adipokines which impact systemic energy metabolism. Brown adipocytes have a striking capacity for clearing circulating lipids and glucose from the bloodstream, and multiple mouse models have demonstrated that increasing BAT activity dramatically improves whole-body insulin sensitivity and glucose homeostasis. Therefore, BAT is considered a target for preventing and treating obesity and diabetes.

We have carried out chemical compound screens to identify novel regulators of brown adipocyte biology, e.g. thermogenesis and adipokine secretion. The screens revealed targets that were required for brown adipocyte thermogenesis and targets that restricted thermogenesis. We identified numerous novel brown adipocyte regulators and are currently studying a number of these, including signaling proteins and adipokines (Knoll et al., 2017; Markussen et al., 2018). We focus on druggable targets that restrict energy metabolism in our recently established human brown adipocyte cell model (Markussen et al., 2017), as inhibition of such targets may further increase energy dissipation by human adipocytes. 

If you are interested in obesity research, cellular signaling, brown adipocytes and human cell models, contact group leader Jacob B. Hansen for more information.

Anvendte metoder:Cell culture, real-time quantitative PCR, large-scale gene expression profiling, immunoblotting, real-time cellular respiration (Seahorse XF96 Flux Analyzer), siRNA/shRNA-mediated gene silencing, siRNA and compound screens, retro- and lentivirus-mediated overexpression, primary cell isolation
Keywords:Energy expenditure, metabolism, oxygen consumption, cellular signaling, transcriptional regulation
Vejleder(e): Jacob B. Hansen