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Ω3 Fatty Acids Activate Ciliary FFAR4 to Trigger Adipogenesis in Perivascular Preadipocytes

47 Pages Posted: 2 Oct 2018 Publication Status: Under Review

See all articles by Keren I. Hilgendorf

Keren I. Hilgendorf

Stanford University - Baxter Laboratory in Stem Cell Biology

Carl T. Johnson

Stanford University - Baxter Laboratory in Stem Cell Biology

Anja Mezger

Stanford University - Department of Genetics

Janos Demeter

Stanford University - Department of Pathology; Stanford University - Baxter Laboratory in Stem Cell Biology

William J. Greenleaf

Stanford University - Department of Applied Physics

Peter K. Jackson

Stanford University - Baxter Laboratory in Stem Cell Biology; Stanford University - Department of Pathology

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Abstract

Recent studies find that mesenchymal progenitor cells including preadipocytes are ciliated and primary cilia are required for adipogenesis. The signaling function and location of ciliated cells in fat are unknown. We discover that ciliated preadipocytes abundantly populate a perivascular compartment in fat and are activated by high fat diet. We show Tulp3-dependent ciliary receptor trafficking is required for adipogenesis and identify the ω3 fatty acid receptor Ffar4/Gpr120 as the Tulp3-dependent ciliary GPCR. Ffar4 agonists and ω3 fatty acid DHA trigger mitogenesis and adipogenesis. DHA or FFAR4 agonists, but not saturated fatty acids, rapidly activate cAMP production inside cilia to activate EPAC signaling, induce CTCF-dependent chromatin remodeling, promote transcriptional activation of Pparγ/Cebpα, and initiate adipogenesis. DHA can replace cAMP activators to trigger adipogenesis. We propose dietary ω3 fatty acids selectively drive expansion of adipocyte numbers ensuring production of new fat cells to balance storage of saturated fatty acids, allowing homeostasis of heathy fat tissue.

Suggested Citation

Hilgendorf, Keren I. and Johnson, Carl T. and Mezger, Anja and Demeter, Janos and Greenleaf, William J. and Jackson, Peter K., Ω3 Fatty Acids Activate Ciliary FFAR4 to Trigger Adipogenesis in Perivascular Preadipocytes (October 2, 2018). Available at SSRN: https://ssrn.com/abstract=3259133 or http://dx.doi.org/10.2139/ssrn.3259133
This version of the paper has not been formally peer reviewed.

Keren I. Hilgendorf

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

Carl T. Johnson

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

Anja Mezger

Stanford University - Department of Genetics

Stanford, CA 94305
United States

Janos Demeter

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

William J. Greenleaf

Stanford University - Department of Applied Physics

CA
United States

Peter K. Jackson (Contact Author)

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

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