TY - JOUR
T1 - Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages
AU - Yu, Haidong
AU - Dilbaz, Sedat
AU - Coßmann, Jonas
AU - Hoang, Anh Cuong
AU - Diedrich, Victoria
AU - Herwig, Annika
AU - Harauma, Akiko
AU - Hoshi, Yukino
AU - Moriguchi, Toru
AU - Landgraf, Kathrin
AU - Körner, Antje
AU - Lucas, Christina
AU - Brodesser, Susanne
AU - Balogh, Lajos
AU - Thuróczy, Julianna
AU - Karemore, Gopal
AU - Kuefner, Michael Scott
AU - Park, Edwards A
AU - Rapp, Christine
AU - Travers, Jeffrey Bryant
AU - Röszer, Tamás
PY - 2019
Y1 - 2019
N2 - Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.
AB - Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.
U2 - 10.1172/JCI125646
DO - 10.1172/JCI125646
M3 - Journal article
C2 - 31081799
VL - 129
SP - 2485
EP - 2499
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 6
ER -