Hepatic depletion of ACLY but not of ACSS2 results in upregulation of enzymes in the DNL pathway processed (active) SREBP1c protein levels. Livers from the HFD-fed mouse groups were processed for investigation of (A) mRNA and (B) protein expression changes between the groups. C, quantification of protein levels between groups. (ns, not significant, ∗p < 0.05, ∗∗p < 0.005, ∗∗∗p < 0.0005, and ∗∗∗∗p < 0.00005). ACLY, ATP-citrate lyase; ACSS2, AcCoA synthase short-chain family member 2; DNL, de novo lipogenesis; HFD, high-fat diet; SREBP1c, sterol regulatory element–binding protein 1c.