Have you ever wondered how mitochondrial and cytosolic pathways for de novo lipogenesis (DNL) interact? We did! Published Online today (cell.com/cell-metabolism/ful…) and led by first-author @adam_rauckhorst, we traced 13C-labeled lactate/pyruvate, acetate, the ketone acetoacetate, and leucine in several mouse models of disrupted hepatic mitochondrial and cytosolic acetyl-CoA generating pathways. Surprisingly, deleting the mitochondria citrate carrier (CiC) increased DNL from both exogeneous and leucine-generated acetoacetate. Overall, our findings delineate a mitochondrial-cytosolic DNL substrate supply network that may guide more accurate therapeutic development for MASLD and T2D. Many thanks to our expert collaborators: No X Ryan Sheldon, now leading metabolomics at the @VAInstitute, who helped start the project and develop the necessary mass spec methods with @adam_rauckhorst; for @StanislawDeja and @Isotopomer for deuterium tracing by NMR and careful contibutions to quantitatively framing our mass spec data; and Tom Vallim of @TarlingVallim for guidance with in vivo gene deletion by AAV CRISPRs. Please also see the exciting co-published manuscript from @WellenLab and Christian Metallo Labs (cell.com/cell-metabolism/ful…) showing that bempadoic acid does more than just inhibit ACLY! @FOEDRC, @UIowaResearch, @UIMolecPhysBio