Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity.
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.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Yang
Y
Du
Marie
M
Yang
Syann
S
Lee
Cassie L
CL
Behrendt
Lora V
LV
Hooper
Alan
A
Saghatelian
Yihong
Y
Wan
D000818:Animals; D000831:Animals, Newborn; D002518:Ceramides / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005856:Germ-Free Life / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D007774:Lactation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism / Q000633:toxicity*; D009035:Mothers; D011247:Pregnancy; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019366:Western World
D002518:Ceramides; D005227:Fatty Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4