Patrick Lundgren (Mentor: Christoph Thaiss, PhD)

“Adipocyte division of labor mediates thermogenic memory”

Patrick Lundgren, Prateek Sharma, Jacqueline Chan, Aravind Krishnan, Hélène Descamps, Lenka Dohnalová, Klaas Bahnsen, Yael Heyman, Patrick Seale and Christoph Thaiss

The formation of memory in response to transient environmental stimuli is important for animals to survive and reproduce in their environment. On an organismal level, memory has mostly been studied in the context of the immune and nervous systems in response to for example infection or experience. However, the mechanisms that underlie altered responses to transient shifts in abiotic factors such as temperature remain poorly understood. Here, we find that a transient acute cold exposure leads to tissue-specific transcriptional and metabolic reprogramming in brown adipose tissue, which is critical to an improved secondary thermogenic response to acute cold. In particular, we find large-scale remodeling of lipid metabolism in brown adipose tissue following a primary cold challenge, with induction of de novo lipogenesis which importantly does not require continuous cold exposure. Further, we discover that a primary thermogenic response induces a population of lipogenic adipocytes in brown adipose tissue, which are largely distinct from thermogenic adipocytes, and when lipogenesis is inhibited ablates an improved secondary thermogenic response. Overall, our data highlights the importance of heterogenous adipocyte populations in brown adipose tissue in the physiologically relevant setting of repeated cold exposures, which may have implications for the therapeutic efforts to leverage thermogenesis to neutralize the hypercaloric state of obesity.