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Dynamic subcellular proteomics identifies regulators of adipocyte insulin action
Olivia J Conway1, Josie A Christopher2, Lisa M Breckels2
1Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Nature Communications
|March 1, 2026
Summary
Insulin triggers widespread protein movement within fat cells (adipocytes) to regulate metabolism. A newly identified protein, C3ORF18, is crucial for maintaining fat cell insulin sensitivity.
Area of Science:
- Cell biology
- Metabolic research
- Proteomics
Background:
- Insulin signaling in adipocytes controls glucose and lipid metabolism by regulating protein localization.
- The full extent and importance of insulin-stimulated protein relocalization in adipocytes remain unclear.
Purpose of the Study:
- To comprehensively map acute insulin-stimulated protein relocalization in adipocytes.
- To investigate the role of uncharacterized proteins in the cellular insulin response.
Main Methods:
- Subcellular proteomics approaches were employed to analyze protein localization changes.
- Quantitative analysis of protein redistribution in response to insulin stimulation.
Main Results:
- Extensive insulin-regulated protein redistribution was observed, involving hundreds of proteins.
- The uncharacterized protein C3ORF18 was identified to redistribute to the plasma membrane upon insulin stimulation.
- Depletion of C3ORF18 impaired adipocyte insulin sensitivity.
Conclusions:
- Insulin stimulation induces large-scale protein relocalization within adipocytes.
- C3ORF18 plays a significant role in maintaining adipocyte insulin sensitivity.
- The study provides a valuable resource for understanding protein localization's role in cellular insulin responses.
