Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer
Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer
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DOI：
10.1073/pnas.012610299
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发表时间：
2002-01-08
影响因子：
11.1
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Barak, Y;Liao, D;Evans, RM
通过同源重组靶向前列腺素受体过氧化物酶体增殖物激活受体增量(PPARDelta)导致胎盘缺陷和频繁的(90%)中期死亡。与野生型相比，存活的PPARDelta(-/-)小鼠的肥胖率显著降低。这种效应不能在脂肪组织特异性缺失PPARDelta的小鼠身上再现，因此可能反映了外周PPARDelta在全身脂质代谢中的功能。最后，我们观察到PPARDelta对于APC(Min)小鼠肠和结肠息肉的形成是必不可少的，这与它最近提出的在建立结直肠肿瘤中的作用不一致。总之，这些观察揭示了PPARDelta在胚胎发育和脂肪细胞生理中的特定作用，但不是在癌症中。
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.