DCHP targets lipid associated macrophages to disrupt lipid metabolism via crosstalk with adipocyte precursor cells

The role of lipid associated macrophages (LAMs) in metabolic homeostasis remains an important yet understudied aspect of adipose tissue. Here, we report a potential new regulatory mechanism by which LAM control adipose tissue homeostasis, involving the endocrine disrupting chemical (EDC) dicyclohexyl phthalate (DCHP) and resulting in altered metabolic regulation. Prepubertal DCHP exposure decreased adipose tissue mass and increased plasma triglycerides in mice. Mechanistically, DCHP facilitated the formation of LAMs. And LAMs communicated with adipocyte precursors, especially adipose progenitor cells, via ApoE-APP interaction, leading to abnormal adipogenesis. Blocking LAMs formation via macrophage-specific PPAR? knockout enabled adaptive adipogenesis, ameliorating DCHP-induced metabolic disorder. Our data highlight the essential role of LAMs in inhibiting adaptive adipogenesis, providing a scientific basis for EDC-induced metabolic dysfunction and phthalates toxicity. Overall design: To investigate the mechanistic regulation of macrophages polarization by Monocyclohexyl phthalate (MCHP), PPRE-eGEP-THP-1 cell line from our previous study was used. Cells were treated with MCHP (100 µM) or corresponding solvent for 24 hours during the polarization of M1 or M2 macrophages. Then, total RNA were extracted with TRIzol for transcriptome sequencing. Biological replicates (n=3/per treat) were used.