Sex and Depot Specific Adipocyte Proteome Profiling In Vivo via Intracellular Proximity Labeling.

Adipose tissue has varying distributions and metabolic properties between the sexes. Inherent sex-specific differences in adipocytes may heighten the risk of metabolic disease in males. Analysis of the adipocyte proteome can potentially provide important insight. To enable cell-type specific proteomic profiling in vivo, we genetically engineered a mouse line for cell-type specific production of a promiscuous biotin ligase (BirAG3) facilitating the rapid isolation of biotinylated cell-type specific proteomes. Adipocyte-specific activation of cytoplasmic BirAG3 led to robust biotinylation of adipocyte proteins across all major fat depots. Comparison of brown adipose tissue (BAT) and subcutaneous white adipose tissue (SAT) proteomes identified 229 brown adipose-enriched and 35 white adipose-enriched proteins. Regional comparison of white fat depots revealed additional differences across depots. Comparison of male and female depots identified sexually dimorphic adipose proteins: AHNAK predominating in the male and ACOT2 in the female. These findings validate the genetic model and highlight insights to be gained through targeted profiling of adipocytes. The genetic tool adds to existing approaches for in vivo proximity profiling of cell-type specific proteome programs.