Editors' ChoiceMetabolism

When fat cells are beige, future is brite

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Science Translational Medicine  05 Jun 2019:
Vol. 11, Issue 495, eaax9559
DOI: 10.1126/scitranslmed.aax9559


Breast milk lipid mediators sustain brite fat development in infants, which may reduce their risk of future obesity.

Body fat or adipose tissue comes in different colors and functions. Beige (also called brite) and brown fat cells metabolize lipids to generate heat while white adipocytes store energy as triglycerides. Studies have shown that beige and brown fat cells counteract obesity and metabolic diseases. In adults, cold temperatures stimulate beige fat formation through an effect on adipose tissue macrophages, a type of immune cell that guard against infection. In a recent study, Yu et al. demonstrated the ability of macrophages to metabolize milk alkylglycerols (AKGs) to an active chemical that in turn drives the macrophage-cytokine–dependent differentiation of beige cells during infancy.

AKGs are naturally occurring lipids in human and mouse milk but not in cow milk, which is the base of most infant formula. To test the role of AKGs in altering body fat composition during infancy, the authors compared the impact of natural breast-feeding, infant formula, and exogenous AKGs intake on adipose tissue differentiation in neonate mice. Both exogenous AKGs and natural breastfeeding up-regulated the hallmarks of brite fat differentiation. Formula-based milk, on the other hand, did not result in beige cell differentiation unless it was supplemented with AKGs. Using loss-of-function in vivo studies, the authors revealed that AKGs induced beige differentiation in a macrophage-dependent manner.

Gene expression analysis and metabolite quantification suggested a crucial role of macrophage platelet–activating factor (PAF) in the sustaining effect of AKGs on beige cell development. Because of the structural similarity between AKGs and PAF and the availability of PAF synthesis enzymes in macrophages but not adipocytes, the authors concluded that macrophages were solely responsible for the metabolism of AKGs into PAF. The story gets tricky, as the authors found that PAF itself lacks a direct beige adipose tissue differentiating effect. PAF may act within macrophages to release the interleukin-6 that ultimately triggers the “beiging” of adipose tissue.

In summary, Yu et al. revealed that the functional state of macrophages at early stage of infant development provides a window of opportunity for breast milk alkylglycerols to be metabolized, dictating the signaling of adipose tissue differentiation. The investigation provides potential mechanistic insights into the well-known protective effect of breast-feeding against childhood obesity.

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