Intracrine FFA4 signaling controls lipolysis at lipid droplets

O'Brien SL
Birmingham University
August 5, 2025
Nat Chem Biol
https://pubmed.ncbi.nlm.nih.gov/40764678

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/40764678

Research summary

The study demonstrates that FFA4 (GPR120) signals intracrinally at lipid droplet membranes to suppress basal lipolysis in adipocytes. Using a Ffar4 conditional Knockout mouse, they showed that adipocyte‑specific deletion of FFA4 disrupts its localization to lipid droplets, enhances lipolysis, and increases fatty acid release. This intracrine role was independent of classical GPCR surface signaling.

Key outcome of the study

Adipocyte‑specific deletion of FFA4 increases lipolysis and fatty acid efflux. FFA4 localizes to lipid droplets and functions independently of surface receptor signaling; identifies novel intracrine GPCR function

Model

Ffar4^flox/flox conditional Knockout mouse, crossed with adipocyte-specific Cre lines — genOway-developed, C57BL/6 background

TARGET:
Ffar4
Synonyms:
GPR120; O3FAR1

Keywords

Lipolysis regulation, adipose tissue metabolism, GPCR intracellular signaling, metabolic disease, fatty acid homeostasis

Technical specifications

Conditional Knockout of Ffar4 (GPCR), adipocyte-specific Cre expression, lipid droplet isolation, live-cell and ex vivo adipose imaging, metabolic assays of fatty acid release

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