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J Clin Invest. 2019 May 13;129(6):2485-2499. doi: 10.1172/JCI125646. eCollection 2019 May 13.

Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages.

Author information

1
Institute of Neurobiology, and.
2
Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany.
3
Department of Food and Life Science, Azabu University, Sagamihara, Kanagawa, Japan.
4
Center for Pediatric Research, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
5
Lipidomics Facility, CECAD Research Center, University of Cologne, Cologne, Germany.
6
Department of Nuclear Medicine, National Public Health Center (NPHC), Budapest, Hungary.
7
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
8
Veterans Affairs Medical Center and the Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
9
Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio, USA.

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.

KEYWORDS:

Adipose tissue; Immunology; Macrophages; Metabolism; Obesity

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