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Maternal PPAR protects nursing neonates by suppressing the production of inflammatory milk
Benjamin F. Cravatt2,, and
Ronald M. Evans1,4
1 Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA; 2 The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
Lactation is a highly demanding lipid synthesis and transportprocess that is crucial for the development of newborn mammals.While PPAR is known to promote adipogenesis and lipogenesisin adipose tissue, its role in the lactating mammary gland isunexplored. Here, we report that a targeted deletion of PPARin mice results in the production of "toxic milk" containingelevated levels of inflammatory lipids. Surprisingly, ingestionof this "toxic milk" causes inflammation, alopecia, and growthretardation in the nursing neonates. Genomic profiling revealsthat PPAR deficiency leads to increased expression of lipidoxidation enzymes in the lactating mammary gland. Consistently,metabolomic profiling detects increased levels of oxidized freefatty acids in the pups nursed by PPAR-deficient mothers. Therefore,maternal PPAR is pivotal for maintaining the quality of milkand protecting the nursing newborns by suppressing the productionof inflammatory lipids in the lactating mammary gland.