E3 UBIQUITIN LIGASE2 SIAH2 MAY REGULATE AGE-ASSOCIATED LIPID TURNOVER IN ADIPOSE TISSUE MACROPHAGES
2024

Siah2 and Lipid Turnover in Aging Macrophages

publication

Author Information

Author(s): Ghosh Bhaswati

Primary Institution: Pennington Biomedical Research Center

Hypothesis

Aging downregulates proteasomal activity in adipose tissue macrophages (ATMs) resulting in dysfunctional lipid metabolism.

Conclusion

Siah2 functions as a critical lipid sensor in ATMs, and aging may lead to decreased Siah2 activity, resulting in reduced lipid turnover.

Supporting Evidence

  • SKM-ATMs accumulate more and larger lipid droplets than WT-ATMs.
  • Siah2KO in ATMs suppresses lysosomal delivery of lipid droplets.
  • SKM-BMDMs are pro-inflammatory and show decreased oxygen consumption rate.

Takeaway

As we get older, a protein called Siah2 in certain immune cells helps manage fat. If it doesn't work well, it can lead to more fat buildup.

Methodology

Generated a macrophage-specific Siah2 knockout mouse model and co-cultured primary bone marrow-derived macrophages with adipose tissue.

Digital Object Identifier (DOI)

10.1093/geroni/igae098.3654

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