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Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages
Haidong Yu, … , Jeffrey Bryant Travers, Tamás Röszer
Haidong Yu, … , Jeffrey Bryant Travers, Tamás Röszer
Published May 13, 2019
Citation Information: J Clin Invest. 2019;129(6):2485-2499. https://doi.org/10.1172/JCI125646.
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Research Article Immunology Metabolism

Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

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Abstract

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.

Authors

Haidong Yu, Sedat Dilbaz, Jonas Coßmann, Anh Cuong Hoang, Victoria Diedrich, Annika Herwig, Akiko Harauma, Yukino Hoshi, Toru Moriguchi, Kathrin Landgraf, Antje Körner, Christina Lucas, Susanne Brodesser, Lajos Balogh, Julianna Thuróczy, Gopal Karemore, Michael Scott Kuefner, Edwards A. Park, Christine Rapp, Jeffrey Bryant Travers, Tamás Röszer

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Figure 6

Effects of dietary AKG supplementation in obesity.

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Effects of dietary AKG supplementation in obesity.
(A) Transcript levels...
(A) Transcript levels of BeAT genes and genes associated with adipogenesis and lipolysis in iAT of lean, and HFD-fed mice, treated with vehicle or AKGs. (B) Histology and UCP1 immunohistochemistry of iAT of HFD-fed mice treated with vehicle or AKGs. Scale bars: 50 μm. (C) Transcript levels of BeAT genes and genes associated with adipogenesis and lipolysis in iAT of Leprdb/db mice treated with vehicle or AKGs. (D) Weight gain within 1 week, iAT weight, and TG content of iAT of Leprdb/db mice treated with vehicle or AKGs. (E) Histology, (F) adipocyte size, and (G) plasma glycerol level in Leprdb/db mice treated with vehicle or AKGs. Scale bars: 50 μm (H&E); 10 μm (UCP1). Arrowheads show UCP1+ adipocyte. (H) NGS analysis of vehicle- and AKG-treated ATMs, showing relative abundance of transcripts. Pink bars, combined score ranking of GO terms. Venn diagram of AKG-suppressed interferon-responsive genes, clustered according to the type of interferon response. (I) Crown-like structures (CLSs) in iAT of Leprdb/db mice treated with vehicle or AKGs. Scale bars: 50 μm. Quantification of CLSs in iAT of Leprdb/db mice treated with vehicle or AKGs. *P < 0.05; **P < 0.01; ***P < 0.001, Student’s 2-tailed unpaired t test.
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