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Sex and Depot Specific Adipocyte Proteome Profiling In Vivo via Intracellular Proximity Labeling
Taylor L Simonian1, Amanda S Meyer1, Jinjin Guo1
1Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Comprehensive Physiology
|April 4, 2025
Summary
Researchers developed a new genetic tool for studying fat cells (adipocytes) in vivo. This method identified sex-specific proteins in male and female adipose tissue, offering insights into metabolic disease risk.
Area of Science:
- Metabolomics
- Proteomics
- Molecular Biology
Background:
- Adipose tissue exhibits sex-specific variations in distribution and metabolism.
- Differences in adipocytes may increase metabolic disease risk in males.
- Adipocyte proteome analysis offers potential insights into these differences.
Purpose of the Study:
- To develop a genetic tool for cell-type specific proteomic profiling in vivo.
- To investigate sex-specific differences in the adipocyte proteome.
- To compare proteomes across different adipose tissue depots.
Main Methods:
- Genetically engineered a mouse line for cell-type specific biotin ligase (BirA*G3) production.
- Activated BirA*G3 in adipocytes for in vivo proximity-dependent biotinylation.
- Compared proteomes of brown adipose tissue (BAT) and subcutaneous white adipose tissue (SAT) from male and female mice.
Main Results:
- Robust biotinylation of adipocyte proteins was achieved across major fat depots.
- Identified 229 brown adipose-enriched and 35 white adipose-enriched proteins.
- Discovered sexually dimorphic adipose proteins: AHNAK (male-predominant) and ACOT2 (female-predominant).
Conclusions:
- The developed genetic model effectively enables targeted adipocyte proteomic profiling in vivo.
- Sexually dimorphic proteins in adipose tissue were identified, contributing to understanding sex-specific metabolic health.
- This tool enhances existing methods for in vivo proximity proteomic analysis.
