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 June 3, 2019; First 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

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 1

Breast milk AKGs increase beige adipocyte content in infant mice.

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Breast milk AKGs increase beige adipocyte content in infant mice. (A) St...
(A) Structure of AKGs found in human breast milk. (B) Level of AKGs in mouse breast milk on P3 and P6 normalized to protein content. (C) Levels of AKGs in breast milk of 3 lactating mice and the plasma AKG levels of their respective litters on P3 and P6. One data point represents plasma pooled from 8 to 9 infant mice. Plasma AKG levels on P56. (D) Schematic of AKG treatment of infant mice. (E) iAT weight on P10 of vehicle- or AKG-treated mice. (F–H) Histology of iAT. H&E staining and UCP1 immunohistochemistry (F), semithin sections stained with toluidine blue (G), and transmission electron microscopy of adipocytes (H). lp, lipid vesicle; mt, mitochondria; nc, nucleus. Arrowheads show BeAT; arrow shows fusing lipid vesicles. Scale bars: 25 μm (F and G); 5 μm (H). (I) Mitochondrial content, TG content, adipocyte size, BeAT area in iAT, plasma glycerol levels, and lean weight on P10. (J) Transcription of BeAT hallmark genes in iAT on P10 of vehicle- or AKG-treated mice. *P < 0.05; **P < 0.01; ***P < 0.001, 1-way ANOVA with Dunnett’s post hoc test (C) and Student’s 2-tailed unpaired t test (E, I, J).