Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis

Primary cilia play a pivotal role in signal transduction and development and are known to serve as signaling hubs. Recent studies have shown that primary cilium dysfunction influences adipogenesis, but the mechanisms are unclear. Here, we show that mesenchymal progenitors C3H10T1/2 depleted of trichoplein, a key regulator of cilium formation, have significantly longer cilia than control cells and fail to differentiate into adipocytes. Mechanistically, the elongated cilia prevent caveolin-1- and/or GM3-positive lipid rafts from being assembled around the ciliary base where insulin receptor proteins accumulate, thereby inhibiting the insulinAkt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockoutmice on an extended high-fat diet exhibit reduced body fat and smaller adipocytes than wild-type (WT) mice. Overall, our results suggest a role for primary cilia in regulating adipogenic signal transduction via control of the lipid raft dynamics around cilia.

Automated summary

This study reveals that depletion of trichoplein, a key regulator of cilium formation, in mesenchymal progenitors results in longer cilia and inhibits adipocyte differentiation. Mechanistically, elongated cilia prevent the formation of lipid rafts around the ciliary base, affecting insulin signaling and adipogenesis. Knockout mice lacking trichoplein show reduced body fat and smaller adipocytes when fed a high-fat diet, indicating the crucial role of primary cilia in regulating adipogenic signal transduction.