Skin lipid homeostasis via acetyl-CoA synthesis
Cytosolic acetyl-coenzyme A (acetyl-CoA) is generated by ATP-citrate lyase (ACLY).
The authors show that ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; deletion of both Acly and Acss2 from the skin exacerbates skin abnormalities, depletes key epidermal barrier lipids, disrupts the skin barrier, and causes rapid fat loss.
However, sebum production by sebaceous glands is sustained using circulating lipids. Dietary fat supplementation further boosts sebum production and partially rescues both the lipoatrophy and the aberrant skin phenotypes.
These findings reveal the vital role of skin acetylCoA synthesis in local and systemic lipid metabolism.
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00055-5
