PPARA and myocardial ischemia: In animal experiments, BCAAs transcriptionally upregulated PPAR-α expression, thereby exacerbated lipid peroxidation toxicity and cardiac ischemia/reperfusion vulnerability.36 BCAAs also regulate the mechanistic target of rapamycin (mTOR) pathway,1 which is crucial for cardiometabolism.37 BMI may also mediate the association of BCAAs with diabetes, however, MR analysis using different analytic methods did not confirm BCAAs affect BMI (Supplemental Table 16).