Brown adipocytes dissipate energy through adaptive thermogenesis. In humans, classical brown adipose tissue (BAT) largely disappears early in life, but cold exposure can induce the formation of brown-like adipocytes within white adipose tissue (WAT), known as brite (brown-in-white) adipocytes. Increased BAT activity elevates energy expenditure and is associated with leanness. Thus, inducing brite adipocytes represents a potential therapeutic approach for treating obesity and related metabolic diseases. However, the molecular mechanisms underlying the specification and activation of brown and brite adipocytes in vivo remain poorly understood.
Using advanced techniques and reporter mice, we generated paired single-mouse datasets and performed an integrative multimodal analysis of five histone marks in beige, brown, and white adipocytes from three distinct mouse adipose tissue depots. Our analysis identified enhancers that distinguish adipocytes by their tissue of origin, differentiating beige from brown adipocytes. Additionally, ablation studies of beige adipocytes revealed that white adipocytes in inguinal adipose tissue and beige adipocytes utilize similar enhancer sets, both preparing thermogenic genes for expression. Conversely, adipocytes from epididymal adipose tissue actively repressed thermogenic master regulators and exhibited a distinct enhancer profile compared to white adipocytes from inguinal tissue. These paired multimodal datasets provide a comprehensive resource for further exploration of the mouse adipocyte epigenome, potentially facilitating the discovery of regulatory elements that govern adipocyte identity and gene regulation.
