Extended Data Fig. 2: In vitro and in vivo data from initial studies (A and B) and a raised therapeutic hypothesis (C).
A. Skin fibroblasts obtained from a patient with P-TGCV carrying homozygous PNPLA2 mutation (c.696+1G>C)2 were cultured for 48 h in a medium containing 500 μM of several kinds of fatty acids conjugated with bovine serum albumin (BSA). Treatment with capric acid (C10:0) reduces cellular TG contents. Data are expressed as relative TG contents compared with those with control (BSA only) (log2-fold change). Error bars indicate standard error. Following two-sided Student’s t-test between control and each fatty acid, adjusted p-values were calculated using multiple comparison method of Bonferroni. B. This patient received 50-day dietary therapy containing 9.0 g of tricaprin before CTx. Improved RQ and fat oxidation were observed using indirect calorimetry (Aeromonitor AE-300S, Minato Medical Science, Osaka, Japan). Enzymatically measured myocardial TG content was markedly reduced in myocardial specimens obtained from CTx, compared with that obtained before the initiation of tricaprin intake. Error bars indicate standard deviation. P-values were calculated using two-sided Student’s t-test. This study was approved by the Ethics Review Committee of Osaka University Hospital (No. 07148). C. The left panel shows extracellular (plasma) and intracellular metabolism of TG in normal conditions. Several intracellular TG lipases and enzymes hydrolyse TG to supply LCFA for mitochondrial oxidation. In TGCV (middle panel), intracellular TG hydrolysis is defective, leading to TG deposition and energy failure in affected cells. Tricaprin (right panel) may facilitate intracellular TG lipolysis independent of ATGL. Abbreviations: ATGL, adipose triglyceride lipase; CTx, cardiac transplantation; DG, diacylglycerol; HSL, hormone-sensitive lipase; LCFA, long-chain fatty acid; LPL, lipoprotein lipase; MG, monoacylglycerol; MGL, monoacylglycerol lipase; RQ, respiratory quotient; TG, triglyceride; P-TGCV, primary triglyceride deposit cardiomyovasculopathy.
