Researchers Find a Special Lipid that Controls Fat Development in Babies
Researchers discover a lipid in breast milk that functions as a signal in fat tissue to control fat tissue development in babies.
Fat tissue in the body comes in different forms. There is the form that most know, which is called white adipose tissue (WAT for short). WAT is the form that stores fat. There is also a type called brown adipose tissue (BAT for short). This type of fat tissue actually burns energy to help control body temperature when it is cold. The third type is called beige adipose tissue (BeAT). BeAT is related to WAT developmentally, but BeAT functions like BAT in producing heat to regulate body temperature. Both BAT and BeAT are thermogenic (heat-producing) types of fat rather than energy-storing type of fat.
Babies are born with large amounts of BeAT in their fat tissue. Over time, the adipose tissue changes from mostly BeAT cells to mostly WAT cells (Figure 1).
This change corresponds to the changing needs of the child. As children grow, they are better able to regulate body temperature and begin to eat less frequent meals, requiring fat storage rather than fat burning to produce heat. In obese children, the switch from BeAT cells to WAT cells happens earlier than in children with healthy weight.
An international team of researchers identified a lipid that is only found in breast milk and not in other food sources. They detected lipids called 1-O-alkyl-sn-glycerols (abbreviated AKG, Figure 2) in milk from other mammals, including goats, dogs, and mice. However, raw cow’s milk lacked detectable AKG. AKG is not present in formula preparations for babies. Importantly, in addition to the milk from dogs and goats, mice also secrete AKG into their milk. Thus, the scientists could perform studies with mice to understand the role of this lipid in fat tissue development.
In studies of both baby mice and breastfed infants, AKG accumulated in the fat tissue and receiving AKG altered fat development. Fat tissue from mice receiving extra AKG had less WAT and more BeAT. These mice better maintained their body temperature when put into a cold environment. Even after the weaned, the mice that received AKG for 1 week had differences in their fat tissue.
Fat tissue from babies who were breastfed or formula fed was different. Formula currently does not include AKG. The breastfed babies had fat tissue with more BeAT than did the fat tissue from the formula-fed babies. Thus, the presence of AKG in breast milk appears important for human fat development.
To better understand how the lack of AKG altered fat development, the researchers returned to the mice. They divided the mice into 3 groups: one group was nursed by their mothers, another was raised by a non-lactating female mouse and given formula without AKG, and the last group was also raised by a non-lactating female mouse and received formula supplemented with AKG. The fat tissue of the mice receiving the formula without AKG changed from BeAT to WAT earlier than it changed in the mice that were fed by their mothers or that received AKG supplemented-formula. Thus, AKG is important for preventing a premature switch from BeAT to WAT.
This study indicates that AKG is a missing component of infant formula and addition of this lipid would improve temperature regulation in formula-fed infants and could reduce the chance of formula-fed children from developing obesity.
Another interesting finding is that lean healthy adult mice given AKG had no change in their fat tissue. However, obese mice who were fed a high-fat diet had a change in their WAT. The tissue became more like BeAT. Furthermore, compared with the control obese mice, the obese mice receiving AKG gained less weight, had smaller individual fat cells (called adipocytes), and had less fat stored in the adipocytes.
The authors determined that the effects of AKG required a type of immune cell called tissue-resident macrophages that are present in the fat tissue. The fat cells themselves did not respond directly to AKG. Macrophages had to be present. The macrophages of infant mice and obese adult mice are different from those in lean healthy adult mice. Thus, explaining why the lean adult mice were unaffected by adding AKG to their diet.
This research identified a complex signaling system. The mother produced AKG and released it into the breast milk, which was consumed by the baby. In the baby, AKG accumulated in the fat tissue where macrophages converted it into a signal that the macrophages themselves detected. Once stimulated by their own signal, the macrophages released a signal that prevented BeAT cells from switching into WAT cells. As babies mature and have a healthy weight, they stop breast feeding and their macrophages change, allowing most BeAT to make the switch to WAT. In obese children, this switch occurs too soon and formula feeding may be a contributing factor.
H. Yu, S. Dilbaz, J. Coßmann, A. C. Hoang, V. Diedrich, A. Herwig, A. Harauma, Y. Hoshi, T. Moriguchi, K. Landgraf, A. Körner, C. Lucas, S. Brodesser, L. Balogh, J. Thuróczy, G. Karemore, M. S. Kuefner, E. A. Park, C. Rapp, J. B. Travers, T. Röszer, Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages. J Clin Invest. 129, 2485–2499 (2019). https://doi.org/10.1172/JCI125646
Also of Interest
N. R. Gough, Signal or Nutrient: Breast Milk Lipids in Macrophages. BioSerendipity (10 December 2019) https://www.bioserendipity.com/signal-or-nutrient-breast-milk-lipids-in-macrophages