A Cell-Autonomous Cold Sensor Promotes Lipolysis Through Phase Separation

Cooling subcutaneous adipose tissue to 27–31 oC enhances lipolysis via cell-intrinsic liquid-liquid phase separation of PLIN1, enabling PKA recruitment and droplet remodeling.

• Why it matters: Canonical cold adaptation relies on peripheral sensory neurons and sympathetic signaling, leaving a gap for how adipocytes themselves sense physiologically relevant cooling to tune lipolysis.
• What they did: The study shows cooling drives LLPS of perilipin 1 (PLIN1), promoting condensation and local PKA recruitment, which selectively amplifies PKA-mediated perilipin 1 phosphorylation, CGI-58 release, and ATGL-dependent lipolysis.
• The result: An IDR with four conserved aromatic residues is required for cooling-induced LLPS and lipolysis in vivo, and LLPS-competent PLIN1 delivery to inguinal adipose tissue in mice increases local lipolysis and reduces depot mass.