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. This evidence concerns the gene PPARA and obesity due to melanocortin 4 receptor deficiency.