In contrast, DEGs enriched in HFD‐fed mice, including Fabp4, Apoa1, Cyp4a14, Acaa1b, Rxra, Cpt2, Hacd1, Cyp4a32, Acnat1, Acot1, Acnat2, Pltp, and Jak3 were significantly and positively associated with obesity‐abundant bacteria, such as Mucispirillum schaedleri, Lachnospiraceae bacterium 28‐4, Anaerotruncus sp. Here, ACOT1 is linked to obesity due to melanocortin 4 receptor deficiency.