Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity

Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity in mice and human, but the molecular mechanisms that drive BAT cell remodeling remain largely. Using a multilayered approach, we comprehensively map a deep reorganization in the BAT cells. We uncovered a subset of macrophages as the lipid-associated macrophages (LAM), which were massively increased in genetic and dietary model of BAT expansion. LAM participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically-stressed brown adipocytes. CD36 scavenger receptor drives LAM phenotype and through in vitro and in vivo models, we demonstrated that CD36-deficient LAM increased brown fat genes. LAM release Tgf1 that reduces brown adipocytes identity through Aldh1a1 induction. This study provides the first description of cell dynamics in BAT of obese models identifying LAM as responder to tissue-level metabolic stress and key driver to loss of BAT cell identity.