In conclusion, this study is the first to (i) investigate the modulation of Olfr734 in the development of MASLD; (ii) establish a link between asprosin signaling-induced liver steatosis and a Sirt/ER stress pathway; and iii) associate the hepatic levels of OR4M1 with patients with T2DM. Here, OR4M1 is linked to type 2 diabetes mellitus.