Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Daisuke Katoh
Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Kousuke Kasahara
Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Takashi Shiromizu
Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Makoto Matsuyama
Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama 701-0202, Japan
Chise Matsuda
Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Yumi Maeno
Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Masatoshi Watanabe
Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Yuhei Nishimura
Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
Masaki Inagaki
Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; Corresponding author
Summary: 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 insulin-Akt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockout mice 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.