Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.
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AbstractEpidemiologically, 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) alpha agonist, bezafibrate, or a PPARgamma agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in the mice, with induction of LPL mRNA. PPARalpha and PPARgamma 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. PPARalpha and PPARgamma agonists, as well as NO-1886, could be useful as chemopreventive agents for colon cancer.
CitationBiol. Chem. 2006, 387 (4):381-385
DescriptionKEYWORDS CLASSIFICATION: administration & dosage;agonists;Age Factors;Animals;blood;Benzamides;Bezafibrate;Cyclooxygenase 2;deficiency;drug therapy;enzymology;Genes,Apc;Humans;Hyperlipidemias;Intestinal Polyps;Japan;Lipase;Lipoprotein Lipase;metabolism;mechanisms of carcinogenesis;Membrane Proteins;Mice;Organophosphorus Compounds;pharmacology;prevention & control;PPAR alpha;PPAR gamma;Proteins;Research;Thiazolidinediones;Triglycerides.
- Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886, increasing lipoprotein lipase activity in Min mice.
- Authors: Niho N, Mutoh M, Takahashi M, Tsutsumi K, Sugimura T, Wakabayashi K
- Issue date: 2005 Feb 22
- Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands.
- Authors: Niho N, Takahashi M, Kitamura T, Shoji Y, Itoh M, Noda T, Sugimura T, Wakabayashi K
- Issue date: 2003 Sep 15
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- Authors: Takeuchi Y, Takahashi M, Sakano K, Mutoh M, Niho N, Yamamoto M, Sato H, Sugimura T, Wakabayashi K
- Issue date: 2007 Aug
- Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand.
- Authors: Niho N, Takahashi M, Shoji Y, Takeuchi Y, Matsubara S, Sugimura T, Wakabayashi K
- Issue date: 2003 Nov
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