TMAO can bind to R-like endoplasmic reticulum kinase (PERK), selectively activating the PERK branch of the unfolded protein response, which induces the transcription factor FoxO1, a key driver of metabolic diseases in a PERK-dependent manner, and consequently leads to metabolic disturbances such as elevated blood glucose and insulin resistance in mice, both of which are significant risk factors for MASLD [195]. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.