In concordance with the decrease in butyrate, we observed obesity-related downregulation of Acyl-CoA synthetases (Acss1, Acss2, and Acsm3) and Acyl-CoA dehydrogenase (Acadsb) that are specifically responsible for short- and medium-chain fatty acid activation and dehydrogenation during fatty acid oxidation (Table S2A). Here, ACSM3 is linked to obesity due to melanocortin 4 receptor deficiency.