Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
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Michihiro Mutoh
Abstract
Epidemiologically, a high-fat diet is associated with the risk of colon cancer. In addition, serum levels of triglycerides (TGs) and cholesterol have been demonstrated to be positively associated with colon carcinogenesis. We recently found that an age-dependent hyperlipidemic state (high serum TG levels) exists in Apc-deficient mice, an animal model for human familial adenomatous polyposis. The mRNA levels of lipoprotein lipase (LPL), which catalyzes TG hydrolysis, were shown to be downregulated in the liver and intestines of mice. Moreover, treatment with a peroxisome proliferator-activated receptor (PPAR) α agonist, bezafibrate, or a PPARγ agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in the mice, with induction of LPL mRNA. PPARα and PPARγ agonists are reported to exert anti-proliferative and pro-apoptotic effects in cancer cells. One compound that also increases LPL expression levels but does not possess PPAR agnostic activity is NO-1886. When given at 400 or 800 ppm in the diet, it suppresses both hyperlipidemia and intestinal polyp formation in Apc-deficient mice, with elevation of LPL mRNA. In conclusion, a decrease in serum lipid levels by increasing LPL activity may contribute to a reduction in intestinal polyp formation with Apc deficiency. PPARα and PPARγ agonists, as well as NO-1886, could be useful as chemopreventive agents for colon cancer.
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©2006 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
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Artikel in diesem Heft
- Highlight: chronic oxidative stress and cancer
- Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
- Does Helicobacter pylori cause gastric cancer via oxidative stress?
- Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis
- Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
- Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
- Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells
- Evidence for attenuated cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine removal in cancer patients
- The roles of ATP in the dynamics of the actin filaments of the cytoskeleton
- Chiral distinction between the enantiomers of bicyclic alcohols by UDP-glucuronosyltransferases 2B7 and 2B17
- A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms
- Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function
- Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue
- BID, an interaction partner of protein kinase CK2α
- Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity
- Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling
- Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
- A fluorescence assay for rapid detection of ligand binding affinity to HIV-1 gp41