Maternal PPARγ protects nursing neonates by suppressing the production of inflammatory milk

被引:95
作者
Wan, Yihong
Saghatelian, Alan
Chong, Ling-Wa
Zhang, Chun-Li
Cravatt, Benjamin F.
Evans, Ronald M.
机构
[1] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
关键词
PPARg; mammary gland; lactation; inflammation; alopecia; lipid oxidation;
D O I
10.1101/gad.1567207
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Lactation is a highly demanding lipid synthesis and transport process that is crucial for the development of newborn mammals. While PPAR gamma is known to promote adipogenesis and lipogenesis in adipose tissue, its role in the lactating mammary gland is unexplored. Here, we report that a targeted deletion of PPAR gamma in mice results in the production of "toxic milk" containing elevated levels of inflammatory lipids. Surprisingly, ingestion of this "toxic milk" causes inflammation, alopecia, and growth retardation in the nursing neonates. Genomic profiling reveals that PPAR gamma deficiency leads to increased expression of lipid oxidation enzymes in the lactating mammary gland. Consistently, metabolomic profiling detects increased levels of oxidized free fatty acids in the pups nursed by PPAR gamma-deficient mothers. Therefore, maternal PPAR gamma is pivotal for maintaining the quality of milk and protecting the nursing newborns by suppressing the production of inflammatory lipids in the lactating mammary gland.
引用
收藏
页码:1895 / 1908
页数:14
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