Figure 4.

Arg-AP profoundly disturbs pancreatic lipid metabolism, which is prevented by cyclophilin D genetic ablation. Mice were subjected to 24 hours Arg-AP. H&E staining (A) shows multiple small vacuoles in pancreas of wt animals with Arg-AP, identified by EM as lamellar bodies (B,C) and lipid droplets (D). Boxed area in (B), showing accumulation of lamellar bodies, is enlarged in (C). Scale bars: 10 μm (A), 6.7 μm (B), and 1.3 μm (C,D). (E). IB analysis of perilipin 2 (PLIN2), a marker of lipid droplets. The narrow white space indicates the lanes are on the same blot but not contiguous. (F-L). Pancreatic tissue triacylglycerols (TAG) and free fatty acids (FFA) were measured with LC-MS and GC-MS as detailed in Methods. Total, saturated, and unsaturated TAG and FFA levels were quantified based on their detailed profiles (see Supplementary Figure 8C,D), normalized per mg protein, and further normalized to wt control mice. (I-L). Effect of Arg-AP on individual FFAs (the numbers of carbons and of double bonds are indicated). Values are mean ± SEM (n = 3). *P < .05 vs wt saline-treated mice; ^#P < .05 vs same treatment in CypD KO mice.