Molecular Target of Piperine in the Inhibition of Lipid Droplet Accumulation in Macrophages

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  • Matsuda Daisuke
    Graduate School of Pharmacy, Kitasato University
  • Ohte Satoshi
    Graduate School of Pharmacy, Kitasato University
  • Ohshiro Taichi
    Graduate School of Pharmacy, Kitasato University
  • Jiang Wei
    National Key Laboratory for Screening of New Microbial Drugs, Institute of Medical Biotechnology, Chinese Academy of Medical Science
  • Rudel Lawrence
    Department of Pathology, Arteriosclerosis Research Program, Wake Forest University School of Medicine
  • Hong Bin
    National Key Laboratory for Screening of New Microbial Drugs, Institute of Medical Biotechnology, Chinese Academy of Medical Science
  • Si Shuyi
    National Key Laboratory for Screening of New Microbial Drugs, Institute of Medical Biotechnology, Chinese Academy of Medical Science
  • Tomoda Hiroshi
    Graduate School of Pharmacy, Kitasato University

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An alkaloid piperine isolated from the Piper Nigrum was found to inhibit lipid droplet accumulation in mouse macrophages, and especially inhibited cholesteryl ester (CE) synthesis (IC50: 25 μM). The metabolism of cholesterol from lysosome to lipid droplet was inhibited with a similar IC50 (18 μM), indicating that the site of inhibition is one of the steps between the lysosomes and the endoplasmic reticulum. Therefore, effects of piperine on acyl-CoA:cholesterol acyltransferase (ACAT) activity in the microsomes prepared from mouse macrophage and liver were studied, to show that the compounds inhibited the activity in both cases (IC50: 9.1, 7.0 μM, respectively). Furthermore, piperine was found to inhibit both ACAT1 and ACAT2 isozymes to a similar extent (IC50: 16, 18 μM, respectively) in cell-based assays using ACAT1- or ACAT2-expressing cells. Thus, it was suggested that piperine inhibited macrophage ACAT to decrease CE synthesis, leading to a reduction of lipid droplets.

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