Characterization of the Anti-Obesity and Anti-Adipogenic Effects of the Limonoid PrieurianinAuthor InfoSocial Media
2010, Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, College of Medicine.
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 (PPARγ).
Knew-Voon Chin, Ph.D. (Committee Chair)
Sonia Najjar, Ph.D. (Committee Member)
Sandrine Pierre, Ph.D. (Committee Member)
Cynthia Smas, M.D.Sc. (Committee Member)
Ivana de la Serna, Ph.D. (Committee Member)
Manohar Ratnam, Ph.D. (Committee Member)
PLTP; NFkB; TNF; Prieurianin
Saunders, R. (2010). Characterization of the Anti-Obesity and Anti-Adipogenic Effects of the Limonoid Prieurianin. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/
Saunders, Rudel. "Characterization of the Anti-Obesity and Anti-Adipogenic Effects of the Limonoid Prieurianin." Electronic Thesis or Dissertation. University of Toledo, 2010. OhioLINK Electronic Theses and Dissertations Center. 23 Apr 2014.
Saunders, Rudel A. "Characterization of the Anti-Obesity and Anti-Adipogenic Effects of the Limonoid Prieurianin." Electronic Thesis or Dissertation. University of Toledo, 2010. https://etd.ohiolink.edu/