It has been found that nobiletin (Kim et al., 2017) and ursolic acid (Li et al., 2014a) ameliorated insulin resistance and takes effects on amplifying glucose uptake through IRS-1/AKT stimulation (Yuk et al., 2018) in treatment of NAFLD; Jwa Kum Whan ameliorated insulin resistance and reduced hepatic triglyceride and cholesterol accumulation via significant triggered the phosphorylation of IRS-1 and PI3K (Lim et al., 2019). Here, IRS1 is linked to metabolic dysfunction-associated steatotic liver disease.