INS and obesity due to melanocortin 4 receptor deficiency: Previous studies have consistently demonstrated that the TMAO pathway is linked mechanistically to multiple cardiovascular and metabolic processes with CVD pathogenesis including the development of atherosclerotic plaque, promotion of adipose tissue inflammation, alteration in macrophage and endothelial cells, plasma lipid abnormalities, insulin resistance, obesity, and enhanced platelet hyperactivity and thrombosis risk, all of which contribute to SMD due to troponin leak1–6,17,21–23.