Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

• Published in: The Journal of clinical investigation Vol. 129; no. 6; pp. 2485 - 2499
• Main Authors: Yu, Haidong, Dilbaz, Sedat, Coßmann, Jonas, Hoang, Anh Cuong, Diedrich, Victoria, Herwig, Annika, Harauma, Akiko, Hoshi, Yukino, Moriguchi, Toru, Landgraf, Kathrin, Körner, Antje, Lucas, Christina, Brodesser, Susanne, Balogh, Lajos, Thuróczy, Julianna, Karemore, Gopal, Kuefner, Michael Scott, Park, Edwards A., Rapp, Christine, Travers, Jeffrey Bryant, Röszer, Tamás
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.06.2019
• Subjects: Adipocytes; Adipocytes, Beige - cytology; Adipocytes, Beige - metabolism; Adipose tissue; Adipose Tissue, White - cytology; Adipose Tissue, White - metabolism; Alcohol; Animals; Babies; Baby foods; Biomedical research; Body fat; Breast milk; Breastfeeding & lactation; Child development; Childhood obesity; Children; Children & youth; Diabetes; Female; Glycerides - genetics; Glycerides - metabolism; Health care; Humans; Infant; Infants; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipids; Macaca mulatta; Macrophages; Macrophages - metabolism; Mice; Mice, Knockout; Milk; Milk, Human - metabolism; Obesity; Platelet-activating factor; Public health; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Germany; Obesity; Adipose tissue; Immunology; Macrophages; Metabolism
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI125646

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.