BACKGROUND: Recent studies reveal an association between the mitochondrial Amidoxime Reducing Component (MTARC) 1 and 2 proteins and metabolism in Mtarc1/2-deficient mice that are resistant to diet-induced obesity; however, the impact of Mtarc1/2 knockout (KO) on the gut microbiota and metabolome has not been explored in the context of sex and diet. The gene discussed is MTARC1; the disease is obesity due to melanocortin 4 receptor deficiency.