2. Academic Validation
  3. Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

  • Cell. 2019 Nov 27;179(6):1289-1305.e21. doi: 10.1016/j.cell.2019.11.005.
Keren I Hilgendorf 1,  Carl T Johnson 2,  Anja Mezger 3,  Selena L Rice 4,  Alessandra M Norris 5,  Janos Demeter 1,  William J Greenleaf 6,  Jeremy F Reiter 7,  Daniel Kopinke 8,  Peter K Jackson 9
Affiliations

Affiliations

  • 1 Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2 Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stem Cell and Regenerative Medicine Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3 Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • 4 Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • 5 Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.
  • 6 Department of Genetics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
  • 7 Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: jeremy.reiter@ucsf.edu.
  • 8 Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: dkopinke@ufl.edu.
  • 9 Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: pjackson@stanford.edu.
PMID: 31761534 DOI: 10.1016/j.cell.2019.11.005
Abstract

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 ω-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 PPARγ and CEBPα to initiate adipogenesis. We propose that dietary ω-3 fatty acids selectively drive expansion of adipocyte numbers to produce new fat cells and store saturated fatty acids, enabling homeostasis of healthy fat tissue.

Keywords

FFAR4; GPR120; adipogenesis; ciliary signaling; diabetes; mesenchymal stem cells; obesity; omega-3 fatty acid; preadipocyte; primary cilia.

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