A) PGC-1α luciferase reporter assays in wild-type or Plin5 knockout mouse L-cells transduced with control (Gfp) or Atgl adenoviruses. Rescue experiments were performed with overexpression of a plasmid harboring mCherry-Plin5. ATGL inhibition was achieved by the addition of 30 μM ATGListatin (ATGLi) (n=6). *p<0.05 vs. veh, #p<0.05 vs. wild-type, @p<0.05 vs. within treatment vehicle. B) PGC-1α luciferase reporters in primary hepatocytes transfected with control (Ctrl) or Plin5 ASOs. Treatment with EX527 (30 μM) was used to inhibit SIRT1 (n=6–12). *p<0.05 vs. veh, #p<0.05 vs Ctrl ASO, @p<0.05 vs within treatment vehicle. C) PGC-1α/PPAR α target gene expression in livers of mice treated with control or Plin5 ASOs and adenoviruses harboring Gfp or Atgl (n=6–8). *p<0.05 vs. GFP, #p<0.05 vs. Con ASO. D) PGC-1α luciferase reporters in wild-type or Plin5 knockout mouse L-cells transfected with an empty mCherry-vector (EV), mCherry-Plin5, mCherry-Plin5-pD, or mCherry-Plin5-pM (n=6). *p<0.05 vs veh, #p<0.05 vs. wild-type, @ p<0.05 vs. veh. treated Plin5-pM cells. E) Confocal imaging of mCherry-Plin5 transfected cells pretreated with vehicle or the PKA inhibitor H89 (15 μM) for 1 hr followed by addition of 8-bromoadenosine 3’,5’-cyclic monophosphate (cAMP; 1mM) for an additional hour. Cells were also transduced with control or shRNA adenoviruses (repeated with 3 individual hepatocyte isolations). F) Livers from 4 and 16 hr fasted mice were harvested and subjected to histological sectioning and immunostaining to detect PLIN5 (n=3).