4.7 Article

Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity

Journal

GENES & DEVELOPMENT
Volume 26, Issue 12, Pages 1306-1311

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.191031.112

Keywords

metabolism; milk; neonatal inflammation

Funding

  1. Basil O'Connor Scholar Award
  2. Burroughs Wellcome Career Award in Biosciences
  3. Searle Scholars Award
  4. Alfred P. Sloan Award
  5. March of Dimes [5-FY10-1]
  6. Welch Foundation [I-1751]
  7. CPRIT [RP100841]
  8. NIH [R01 DK089113, R01 DK070855]
  9. University of Texas Southwestern Medical Center Endowed Scholar Startup Fund

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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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