Nobiletin inhibits apoB100 secretion from HepG2 cells through activation of MAPK/ERK. attenuated dyslipidemia through a reduction in VLDL-triglyceride secretion. Nobiletin prevented hepatic TG accumulation, increased expression of Pgc1α and Cpt1α, and enhanced fatty acid β-oxidation. Nobiletin increased hepatic and peripheral insulin sensitivity and glucose tolerance and dramatically attenuated atherosclerosis in the aortic sinus. Here, INS is linked to metabolic syndrome.