Many studies have provided contrasting results on the negative influence of TMAO levels on metabolic disorders [53], but more recent reviews have suggested potential benefits depending on the sites of accumulation, with some studies showing that TMAO can ameliorate high-fat-diet-induced adiposity by modulating ER stress responses and improving insulin sensitivity in tissues such as skeletal muscle, liver, and pancreatic β-cells [54,55]. This evidence concerns the gene INS and metabolic disease.