TY - JOUR
T1 - Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity
AU - Du, Yang
AU - Yang, Marie
AU - Lee, Syann
AU - Behrendt, Cassie L.
AU - Hooper, Lora V.
AU - Saghatelian, Alan
AU - Wan, Yihong
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Metabolism
KW - Milk
KW - Neonatal inflammation
UR - http://www.scopus.com/inward/record.url?scp=84862615760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862615760&partnerID=8YFLogxK
U2 - 10.1101/gad.191031.112
DO - 10.1101/gad.191031.112
M3 - Article
C2 - 22713870
AN - SCOPUS:84862615760
SN - 0890-9369
VL - 26
SP - 1306
EP - 1311
JO - Genes and Development
JF - Genes and Development
IS - 12
ER -