Transient activation of ciliary CCR2 signaling promotes the initiation of adipogenesis.

Despite extensive evidence linking inflammation to obesity, a clear mechanistic model for how inflammatory signals regulate adipose tissue development remains lacking. Here, using in vitro and in vivo models, we demonstrate that transient primary cilium assembly and cilium-dependent inflammatory signaling in preadipocytes serve as key initiators of adipogenesis. Adipose stem cells transiently activate a ciliary gene program to form ciliated preadipocytes, which subsequently commit to adipogenesis and lose their cilia upon further differentiation. We further show that C-C motif chemokine receptor 2 (CCR2) localizes to the primary cilia of preadipocytes. High-fat diet feeding remodels the adipose tissue microenvironment, elevating the pro-inflammatory chemokine C-C motif chemokine ligand 2 (CCL2), which engages the cilium-localized CCR2 to initiate adipogenesis via an extracellular signal-regulated kinase (ERK)-dependent signaling pathway. Disruption of cilium assembly or interference with the downstream CCL2/CCR2-ERK signaling axis severely impairs adipogenesis. These findings reveal that the transient assembly of primary cilia in preadipocytes establishes a temporally confined window of heightened sensitivity to environmental inflammatory cues, directing cell fate decisions in adipose tissue development.