Given the role of S100A8/A9 in atherosclerosis in both diabetes and obesity-associated myelopoiesis and the subsequent effects of monocytosis on atherosclerosis, targeting S100A8/A9 could be a potential therapeutic target to treat monocytosis and atherosclerosis in metabolic disease. Here, S100A8 is linked to obesity due to melanocortin 4 receptor deficiency.