Piperine, a Component of Black Pepper, Inhibits Adipogenesis by Antagonizing PPARγ Activity in 3T3-L1 Cells

This study investigated the antiadipogenic activity of black pepper extract and its constituent piperine in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms. Both black pepper extract and piperine, without affecting cytotoxicity, strongly inhibited the adipocyte differentiation of 3T3-L1 cells. The mRNA expression of the master adipogenic transcription factors, PPAR gamma, SREBP-1c, and C/EBP beta, was markedly decreased. Intriguingly, mRNA levels of PPAR gamma target genes were also down-regulated. Moreover, a luciferase reporter assay indicated that pipierine significantly represses the rosiglitazone-induced PPAR gamma transcriptional activity. Finally, GST-pull down assays demonstrated that piperine disrupts the rosiglitazone-dependent interaction between PPAR gamma and coactivator GBP. Genome-wide analysis using microarray further supports the role of piperine in regulating genes associated with lipid metabolism. Overall, these results suggest that piperine, a major component of black pepper, attenuates fat cell differentiation by down-regulating PPAR gamma activity as well as suppressing PPAR gamma expression, thus leading to potential treatment for obesity-related diseases.