Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.

2.50
Hdl Handle:
http://hdl.handle.net/10146/57794
Title:
Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.
Authors:
Mutoh, Michihiro; Niho, Naoko; Wakabayashi, Keiji
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) 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.
Citation:
Biol. Chem. 2006, 387 (4):381-385
Journal:
Biological chemistry
Issue Date:
Apr-2006
URI:
http://hdl.handle.net/10146/57794
DOI:
10.1515/BC.2006.051
PubMed ID:
16606335
Additional Links:
http://www.reference-global.com/doi/abs/10.1515/BC.2006.051
Type:
Article
Language:
en
Description:
KEYWORDS 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.
ISSN:
1431-6730
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorMutoh, Michihiro-
dc.contributor.authorNiho, Naoko-
dc.contributor.authorWakabayashi, Keiji-
dc.date.accessioned2009-03-30T07:55:13Z-
dc.date.available2009-03-30T07:55:13Z-
dc.date.issued2006-04-
dc.identifier.citationBiol. Chem. 2006, 387 (4):381-385en
dc.identifier.issn1431-6730-
dc.identifier.pmid16606335-
dc.identifier.doi10.1515/BC.2006.051-
dc.identifier.urihttp://hdl.handle.net/10146/57794-
dc.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.en
dc.description.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.en
dc.language.isoenen
dc.relation.urlhttp://www.reference-global.com/doi/abs/10.1515/BC.2006.051en
dc.subjectApc-deficient miceen
dc.subjectHyperlipidemiaen
dc.subjectIntestinal polypen
dc.subjectLipoprotein lipaseen
dc.subject.meshAge Factors-
dc.subject.meshAnimals-
dc.subject.meshBenzamides-
dc.subject.meshBezafibrate-
dc.subject.meshCyclooxygenase 2-
dc.subject.meshGenes, APC-
dc.subject.meshHumans-
dc.subject.meshHyperlipidemias-
dc.subject.meshIntestinal Polyps-
dc.subject.meshLipoprotein Lipase-
dc.subject.meshMembrane Proteins-
dc.subject.meshMice-
dc.subject.meshOrganophosphorus Compounds-
dc.subject.meshPPAR alpha-
dc.subject.meshPPAR gamma-
dc.subject.meshThiazolidinediones-
dc.subject.meshTriglycerides-
dc.titleConcomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.en
dc.typeArticleen
dc.identifier.journalBiological chemistryen

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