NR1H4 and obesity due to melanocortin 4 receptor deficiency: Although Rezdiffra [5], a thyroid hormone receptor agonist, has been approved by the FDA for MASH, and other drugs like glucagon-like peptide-1 (GLP-1) agonists, steroidal farnesoid X nuclear receptor (FXR) ligands show potential in large randomized trials, high prevalence of MAFLD coupled with obesity, and type 2 diabetes mellitus will persistently impose substantial physical, psychological, and economic burdens on affected individuals [6,7].