We discuss the mechanisms of key regulators in the development of MASLD, including adipose-derived hormones and cytokines, carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), peroxisome proliferator-activated receptor alpha (PPARα), PPARγ, farnesoid X receptor (FXR), as well as other factors such as neural elements that modulate the adipose–liver axis. This evidence concerns the gene NR1H4 and metabolic dysfunction-associated steatotic liver disease.