Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity
- Yang Du1,
- Marie Yang1,
- Syann Lee2,
- Cassie L. Behrendt3,
- Lora V. Hooper3,4,
- Alan Saghatelian5 and
- Yihong Wan1,6
- 1Department of Pharmacology,
- 2Department of Internal Medicine, Division of Hypothalamic Research,
- 3Department of Immunology,
- 4The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 5Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Abstract
For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation and inflammation in the nursing neonates, manifested as alopecia. This neonatal toxicity requires Toll-like-receptors (TLR), but not gut microbiota, because TLR2/4 deletion or TLR4 inhibition confers resistance, whereas germ-free mice remain sensitive. These findings unravel maternal western diet-induced inflammatory milk secretion as a novel aspect of the metabolic syndrome at the maternal offspring interface.
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Footnotes
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↵6 Corresponding author
E-mail yihong.wan{at}utsouthwestern.edu
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.191031.112.
- Received February 29, 2012.
- Accepted May 11, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press