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. Obesity is linked to chronic inflammation and enhanced adipogenesis. Here, the authors show that preadipocytes transiently form CCR2-enriched primary cilia, allowing inflammatory CCL2 to activate ciliary CCR2 and drive ERK-dependent adipogenesis.