Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis

Area of Science:

• Cell Biology
• Metabolism
• Adipose Tissue Biology

Background:

• Adult mesenchymal stem cells, including preadipocytes, feature primary cilia.
• Preadipocytes in perivascular fat are activated by high-fat diets.

Purpose of the Study:

• Investigate if preadipocyte cilia sense external cues for white adipose tissue remodeling.
• Determine the role of cilia in adipogenesis and fat tissue expansion.

Main Methods:

• Utilized mouse models with abolished preadipocyte cilia.
• Examined TULP3-dependent ciliary localization of FFAR4/GPR120.
• Assessed the effects of FFAR4 agonists and fatty acids on adipogenesis and cAMP production.

Main Results:

• Abolishing preadipocyte cilia impaired white adipose tissue expansion.
• TULP3-mediated ciliary FFAR4 localization is crucial for adipogenesis.
• Omega-3 fatty acids, via FFAR4, activate ciliary cAMP, EPAC, and transcription factors (PPARγ, CEBPα) to promote adipogenesis.

Conclusions:

• Dietary omega-3 fatty acids selectively stimulate adipocyte proliferation through ciliary FFAR4 signaling.
• This mechanism expands fat cell numbers for saturated fatty acid storage, supporting healthy fat tissue homeostasis.