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Genes & Dev. 21 (15): 1895-1908

Copyright © 2007 by Cold Spring Harbor Laboratory Press.

Maternal PPAR{gamma} protects nursing neonates by suppressing the production of inflammatory milk

Yihong Wan1, Alan Saghatelian2,3, Ling-Wa Chong1, Chun-Li Zhang1, 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

Abstract: 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.

Key Words: PPARg • mammary gland • lactation • inflammation • alopecia • lipid oxidation

Received for publication May 3, 2007. Accepted for publication June 14, 2007.

3 Present address: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA

4 Corresponding author.

E-MAIL evans{at}salk.edu; FAX (858) 455-1349.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1567207

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