Maternal adiponectin controls milk composition to prevent neonatal inflammation

Endocrinology. 2015 Apr;156(4):1504-13. doi: 10.1210/en.2014-1738. Epub 2015 Jan 15.


Adiponectin is an important adipokine. Increasing evidence suggests that altered adiponectin levels are linked with metabolic and inflammatory disorders. Here we report an important yet previously unrecognized function of adiponectin in lactation by which maternal adiponectin determines the inflammatory status in the nursing neonates. Surprisingly, both maternal adiponectin overexpression in the transgenic mice and maternal adiponectin deletion in the knockout mice lead to systemic inflammation in the pups, manifested as transient hair loss. However, distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte infiltration and production of inflammatory cytokines in the lactating mammary gland. In contrast, adiponectin overabundance increases lipid accumulation in the lactating mammary gland, resulting in excessive long-chain saturated fatty acids in milk. Interestingly, in both cases, the inflammation and alopecia in the pups can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double-knockout pups are resistant. Mechanistically, long-chain saturated fatty acid activation of inflammatory genes is TLR2/4 dependent and can be potentiated by proinflammatory cytokines, indicating that the inflammatory stimuli in both scenarios functionally converge by activating the TLR2/4 signaling. Therefore, our findings reveal adiponectin as a dosage-dependent regulator of lactation homeostasis and milk quality that critically controls inflammation in the nursing neonates. Furthermore, these results suggest that inflammatory infantile disorders may result from maternal adiponectin dysregulation that can be treated by TLR2/4 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Animals
  • Animals, Newborn
  • Cytokines / analysis*
  • Female
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Lactation / metabolism*
  • Lipids / analysis*
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Milk / chemistry*


  • Adiponectin
  • Cytokines
  • Lipids