Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis.
Adult mesenchymal stem cells, including preadipocytes, possess a cellular sensory organelle called the primary cilium. Ciliated preadipocytes abundantly populate perivascular compartments in fat and are activated by a high-fat diet. Here, we sought to understand whether preadipocytes use their cilia to sense and respond to external cues to remodel white adipose tissue. Abolishing preadipocyte cilia in mice severely impairs white adipose tissue expansion. We discover that TULP3-dependent ciliary localization of the omega-3 fatty acid receptor FFAR4/GPR120 promotes adipogenesis. FFAR4 agonists and omega-3 fatty acids, but not saturated fatty acids, trigger mitosis and adipogenesis by rapidly activating cAMP production inside cilia. Ciliary cAMP activates EPAC signaling, CTCF-dependent chromatin remodeling, and transcriptional activation of PPARgamma and CEBPalpha to initiate adipogenesis. We propose that dietary omega-3 fatty acids selectively drive expansion of adipocyte numbers to produce new fatcells and store saturated fatty acids, enabling homeostasis of healthy fat tissue.
View details for DOI 10.1016/j.cell.2019.11.005
View details for PubMedID 31761534
The primary cilium as a cellular receiver: organizing ciliary GPCR signaling.
Current opinion in cell biology
2016; 39: 84-92
The primary cilium is an antenna-like cellular protrusion mediating sensory and neuroendocrine signaling. Its localization within tissue architecture and a growing list of cilia-localized receptors, in particular G-protein-coupled receptors, determine a host of crucial physiologies, which are disrupted in human ciliopathies. Here, we discuss recent advances in the identification and characterization of ciliary signaling components and pathways. Recent studies have highlighted the unique signaling environment of the primary cilium and we are just beginning to understand how this design allows for highly amplified and regulated signaling.
View details for DOI 10.1016/j.ceb.2016.02.008
View details for PubMedID 26926036
View details for PubMedCentralID PMC4828300