Effect of Tricaprin on Cardiac Proteome in a Mouse Model for Triglyceride Deposit Cardiomyovasculopathy

Triglyceride deposit cardiomyovasculopathy (TGCV), a rare cardiovascular disorder caused by genetic or acquired dysfunction of adipose triglyceride lipase (ATGL), is marked by defective intracellular lipolysis that results in excessive accumulation of triglycerides (TGs) in the myocardium and coronary arteries, leading to intractable heart failure (HF). We have developed a specific treatment for TGCV using tricaprin, a medium chain TG, as part of a governmental rare disease project in Japan. We recently reported that tricaprin diet improved cardiac TG metabolism and left ventricular function in an ATGL-knockout (KO) mouse, a mouse model for TGCV. Here, we report the effect of tricaprin on the myocardial proteome of KO mice to elucidate the mechanisms of action of tricaprin at protein expression levels. We compared proteomic changes in the hearts of KO mice fed control or tricaprin diet. Tandem mass tag-based shotgun proteomics identified 1832 proteins common to all sample groups. Whole proteomic distribution in the heart was largely up-regulated in KO mice fed control diet. When using cut-off values (>1.5 or