ACSS2 governs milk fat synthesis in buffalo via a reciprocal positive feedback loop with SREBP1 and PPARG

This study establishes ACSS2 as a critical metabolic checkpoint in the buffalo mammary gland, rather than a passive enzyme. We propose a model where ACSS2 maintains a reciprocal positive feedback loop with SREBP1 and PPARG. By ensuring sufficient acetyl-CoA to suppress INSIG1 and support histone acetylation (implied by nuclear localization), ACSS2 couples substrate availability to the stability of the lipogenic program and cell cycle progression. These findings reveal an evolutionarily conserved metabolic-epigenetic axis essential for high-efficiency lactation in ruminants.