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. 2005 Aug 19;94(11):960–964. doi: 10.1111/j.1349-7006.2003.tb01385.x

Dose‐dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPARγ ligand

Naoko Niho 1,✉, Mami Takahashi 1, Yutaka Shoji 1, Yoshito Takeuchi 1, Satoshi Matsubara 1, Takashi Sugimura 1, Keiji Wakabayashi 1
PMCID: PMC11160263  PMID: 14611672

Abstract

In our previous study, a peroxisome proliferator‐activated receptor γ (PPARγ) agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in Apc 1309 mice at doses of 100 and 200 ppm in the diet. In contrast, it has been reported that doses of 1500 or 2000 ppm of another PPARγ agonist, troglitazone, enhanced colon polyp development in Min mice. In the present study, we therefore investigated the effects of a wide range of pioglitazone doses on both hyperlipidemia and intestinal polyp formation in Min mice. Serum triglycerides and very low density lipoprotein (VLDL) cholesterol in the basal diet group were elevated to levels 13–15 times higher than those in the wild‐type counterparts at 20 weeks of age. They were reduced dose‐dependently by treatment with 100, 200, 400 and 1600 ppm pioglitazone from 6–20 weeks of age with suppression to almost the wild‐type level at the highest dose. Moreover, up‐regulation of the liver mRNA levels for lipoprotein lipase (LPL) was evident in the pioglitazone‐treated animals. Dose‐dependent reduction of intestinal polyps was observed in Min mice given 100–1600 ppm for 14 weeks, total numbers being decreased to 63–9% of the control value. A suppressive effect of pioglitazone on colon polyp formation was also found. The PPARγ agonist, pioglitazone, may thus be a promising candidate chemopreventive agent for colon cancer.

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