| Phospholipid transfer protein (PLTP) is critically important for reverse cholesterol transport (RCT), and its expression level and activity increase when mice are fed a high fat diet. RCT is the process by which accumulated cholesterol from the blood vessel walls, peripheral tissues and macrophages is transported back to the liver for excretion. Interestingly, topoisomerase I inhibitors used in chemotherapy have been shown in our laboratory to dose dependently induced PLTP expression in both in vivo and in vitro studies. Since PLTP transports phospholipid as well as cholesterol into high density lipoprotein (HDL), we asked whether elevated PLTP levels might increase the transfer of drugs into HDL via RCT, thus increasing tumor cells resistance to the drug. However, we found that camptothecin, topoisomerase I inhibitor, does not accumulate in HDL or in other lipoprotein subfractions, thus ruling out the possibility of PLTP mediating the transfer of camptothecin into HDL for liver metabolism.;The limonoid prieurianin, like topoisomerase I inhibitors, has also been shown to dose dependently increase PLTP mRNA and proteins levels, and here we show that prieurianin causes weight loss by reducing food intake in morbidly obese mice and in mice on high-calorie diet. Additionally, prieurianin is anti-adipogenic and (i) inhibits the proliferation and differentiation of preadipocytes into adipocytes, and (ii) induces either dedifferentiation or delipidation of mature adipocytes. Gene expression profiling showed that prieurianin suppresses the expression of a number of genes involved in fat metabolism, and inhibits the transcriptional activity of the adipogenesis master regulators including the CCAAT/enhancer binding proteins (C/EBPs) and the peroxisome proliferator-activated receptor gamma (PPARgamma). |
