Piperine, a component of black pepper, inhibits adipogenesis by antagonizing PPARγ activity in 3T3-L1 cells

J Agric Food Chem. 2012 Apr 18;60(15):3853-60. doi: 10.1021/jf204514a. Epub 2012 Apr 6.


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, PPARγ, SREBP-1c, and C/EBPβ, was markedly decreased. Intriguingly, mRNA levels of PPARγ target genes were also down-regulated. Moreover, a luciferase reporter assay indicated that pipierine significantly represses the rosiglitazone-induced PPARγ transcriptional activity. Finally, GST-pull down assays demonstrated that piperine disrupts the rosiglitazone-dependent interaction between PPARγ and coactivator CBP. 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 PPARγ activity as well as suppressing PPARγ expression, thus leading to potential treatment for obesity-related diseases.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Alkaloids / pharmacology*
  • Animals
  • Benzodioxoles / pharmacology*
  • Cell Differentiation / drug effects
  • Down-Regulation / drug effects*
  • Mice
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Piper nigrum / chemistry*
  • Piperidines / pharmacology*
  • Plant Extracts / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*


  • Alkaloids
  • Benzodioxoles
  • PPAR gamma
  • Piperidines
  • Plant Extracts
  • Polyunsaturated Alkamides
  • piperine