过氧化物酶体增殖物激活受体δ对胎盘形成、肥胖和结直肠癌的影响。
Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer.
作者信息
Barak Yaacov, Liao Debbie, He Weimin, Ong Estelita S, Nelson Michael C, Olefsky Jerrold M, Boland Richard, Evans Ronald M
机构信息
Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):303-8. doi: 10.1073/pnas.012610299. Epub 2001 Dec 26.
Abstract
Targeting of the nuclear prostaglandin receptor peroxisome proliferator-activated receptor delta (PPARdelta) by homologous recombination results in placental defects and frequent (>90%) midgestation lethality. Surviving PPARdelta(-/-) mice exhibit a striking reduction in adiposity relative to wild-type levels. This effect is not reproduced in mice harboring an adipose tissue-specific deletion of PPARdelta, and thus likely reflects peripheral PPARdelta functions in systemic lipid metabolism. Finally, we observe that PPARdelta is dispensable for polyp formation in the intestine and colon of APC(min) mice, inconsistent with its recently proposed role in the establishment of colorectal tumors. Together, these observations reveal specific roles for PPARdelta in embryo development and adipocyte physiology, but not cancer.
摘要
通过同源重组靶向核前列腺素受体过氧化物酶体增殖物激活受体δ（PPARδ）会导致胎盘缺陷和频繁（>90%）的妊娠中期致死率。存活的PPARδ（-/-）小鼠相对于野生型水平，脂肪量显著减少。在具有脂肪组织特异性PPARδ缺失的小鼠中未观察到这种效应，因此这可能反映了外周PPARδ在全身脂质代谢中的功能。最后，我们观察到PPARδ对于APC（min）小鼠的肠道和结肠息肉形成并非必需，这与它最近在结直肠癌发生中所提出的作用不一致。总之，这些观察结果揭示了PPARδ在胚胎发育和脂肪细胞生理学中的特定作用，但在癌症中并非如此。
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