Brown adipose tissue (BAT) is unique in its ability to generate heat by burning fat rather than storing it. BAT can expand its mass, ramp up thermogenic gene expression and increase its oxidative capacity very quickly, but the mechanisms regulating these processes are not well understood. We recently discovered a molecule (bone morphogenetic protein 8b – BMP8B) that is secreted into and around active BAT (Whittle et al. Cell 2012). BMP8B selectively increases BAT sensitivity to adrenergic stimulation, increasing its thermogenic activity. We believe that better understanding of the molecular networks that BMP8b activates will be of great benefit to understanding adrenergic signalling and BAT biology. In this project, the student will generate data in the Vidal-Puig lab to characterizes the pathways triggered by Bmp8b in primary and transformed adipocytes. Phospho-proteomic measurements will be obtained using mass spectrometry, and the effect of Bmp8b on cellular phenotype will be monitored by gene expression arrays. These data will be analyzed using methods developed in the Saez-Rodriguez group at EBI to reconstruct signaling networks by integration of high-throughput omics data and prior knowledge on the pathways, leading to an mechanistic understanding of how Bmp8 controls thermogenesis. Reduced thermogenesis in humans is increasingly shown to correlate with obesity and ageing, making mechanisms that increase BAT activity extremely relevant to metabolic research. Additionally, knowledge of this previously unknown pathway will have implications for physiological systems controlled by the sympathetic nervous system and be of relevance to a range of metabolic changes associated with ageing.
- Whittle AJ, et al. (2012). BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions. Cell, 149(4):871-85
- Whittle A,et al (2013). Pharmacological strategies for targeting BAT thermogenesis. Trends Pharacol Sci, 34(6):347-55