We showed that spilanthol significantly inhibits the adipogenic proteins C/EBPα, C/EBPβ, PPARα, PPARγ, and SREBP-1 in the liver, and that spilanthol has notable effects against obesity and associated metabolic abnormalities, such as insulin resistance and hyperlipidemia. Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.