Mother's Fat Sends Love Letter to Baby via the Milk Express

"Neither snow nor rain nor heat nor gloom of night…"

Mother's milk allows mothers to nurse infants in environments 

that would otherwise be inhospitable to young. 

Too bad for reptiles.

Body fat is not just for buffering us from famine, keeping us warm during winter, and causing our self-recrimination during swimsuit season. Our body fat is also an integral part of our endocrine signaling system. Hormones that are secreted from fat cells- leptin, for example - communicate with the brain triggering hunger (food!) and cravings for calorie rich foods (cheeseburger!). These hormones also contribute to the processes by which we metabolize and assimilate ingested food. The discovery of these hormones occurred relatively recently, and much remains unknown about their function.  Among the emerging literature, however, are compelling insights into maternal hormones, their transfer via expressed milk, and their consequences in the developing neonate.

I can haz Reubens cheezburger

One such molecule that is gaining attention is adiponectin, first described in 2001. This hormone has anti-inflammatory properties and breaks down fatty acids, but adiponectin is particularly important in its role for increasing sensitivity to insulin. Individuals that have healthier metabolisms and lower BMI have higher circulating adiponectin, whereas heavier individuals have lower circulating adiponectin. In the mammary gland, adiponectin is secreted directly from the adipose tissue and enters milk. There is only a very low correlation between adiponectin concentrations circulating in blood and the levels found in milk. In humans, about 14% of the variation in milk adiponectin is explained by circulating levels in the blood, suggesting that adiponectin is differentially regulated in the mammary gland than elsewhere in the body. Additionally, humans have adiponectin receptors in their intestinal tract, revealing a pathway by which maternal hormonal signals can influence metabolic pathways in the developing infant. Recently, two studies provided important clues about the milk adiponectin and what it may mean in terms of infant development.

adiponectin molecule… supposedly.

In a large (N=170), well-controlled sample of Canadian mothers, Ley and colleagues  showed that in the first week post-partum, adiponectin concentrations in milk are significantly higher than at 3 months post-partum, 50ng/mL vs. 12.3ng/mL. Interestingly, adiponectin concentrations in milk during lactation were not associated with maternal metabolic condition during pregnancy, measured by variables such as body mass index (BMI) and response to oral glucose tolerance test. Other maternal attributes, including socio-economic status, parity, age, ethnicity, physical activity index, and smoking, were covariates in the models. Maternal adiponectin concentrations in serum during pregnancy did predict milk concentrations in the first week post-partum, but only to a minor extent. Similarly, first-time mothers, mothers with a longer gestation, and mothers that had an unscheduled c-section had higher concentrations of adiponectin in milk during the first week post-partum. Why these mothers had higher concentrations of adiponectin was not clear. One explanation is that first-time mothers and women that undergo c-section are more likely to experience delayed onset of copious milk production (aka lactogenesis II or secretory activation). Ley and colleagues did not measure milk volume, but higher adiponectin concentrations may be an artifact if these mothers were producing less milk, and it’s likely they were. This may also explain why adiponectin concentrations decrease from the first days of lactation, when many mothers are producing colostrum, to the lower concentrations found in mature milk at 3 months when mothers produce higher volumes of milk.

But what does adiponectin do when ingested by the infant? In an even larger (N=192), similarly well-controlled study, Woo and colleagues  investigated monthly adiponectin concentrations in milk across the first 5 months of lactation in a sample of mothers and infants in Mexico City. The first exciting result was that the adiponectin concentrations were substantially higher in the mature milk of the mothers in Mexico City compared to the levels found among mothers in Canada. The sample mean from 1-5 months varied by ~22±5 ng/mL. The Canadian women, on average, were older but of relatively similar parity. Unfortunately, BMI was not reported so could not be compared between the two studies. Inter-population differences could be the result of many factors and warrant further investigation. However, even more fascinating, Woo et al. revealed that infants consuming milk with higher concentrations of milk adiponectin weighed less for their age and length from 1-6 months of age than did infants consuming lower levels of milk adiponectin. But during their second year of life, infants who had consumed higher levels of adiponectin demonstrated accelerated growth; gaining more weight for their age and height than did infants who had consumed low adiponectin milk.

Best Map I could find of Canada and Mexico

The underlying mechanisms driving the relationship between milk adiponectin and infant growth trajectories are unclear. These data suggest that higher adiponectin in milk slows growth during early development (through reduced appetite?), but then accelerates during the second year of life when they are no longer exclusively breast-feeding and instead consuming primarily solid foods. From an evolutionary perspective, this makes perfect sense. We would predict that milk contains hormonal elements that slow growth or reduce infant appetite in order to reduce the energetic burden on mothers to mobilize body stores for milk synthesis. Every dairy farmer can tell you lactation demands substantial energy expenditure, and the greater the expenditure, the greater the depletion of maternal resources. Depletion delays the ability to conceive subsequently, lengthening inter-birth intervals, and consequently, mothers produce fewer babies in their reproductive career (causing Natural Selection to make a frowny face). So it could be very adaptive for mother’s milk to contain hormones that reduce infant growth when they are reliant on milk but that enable them to catch up when they transition to solid foods and won’t be depleting their mother.

Flemish Dairy Farm, Jan Brueghel il Vecchio

However, before I get too carried away getting jazzed about natural selection and adaptations, allow me to exercise some caution. These data are correlational and there may be alternative explanations for the effects described above. For example, adiponectin concentrations in mature milk are negatively correlated with milk glucose (the relationship is weak, but significant), so other milk parameters may be a factor that contributes to infant growth trajectories.

Clearly there is much we still need to understand about the relationship among milk constituents and their functions in the developing infant (AKA: my take home message for pretty much every post).

1. Savino F, Liguori SA, Fissore MF, Oggero R. 2009. Breast milk hormones and their protective effect on obesity. Int J Pediatr Endocrinol. Epub 327505. doi: 10.1155/2009/327505

2. Woo JG, Guerrero ML, Guo F, Martin LJ, Davidson BS, Ortega H, Ruiz-Palacios GM, Morrow AL. 2012. Human milk adiponectin affects infant weight trajectory during the second year of life. J Pediatric Gastroenterology Nutr. 54: 532-539

3. Ley SH, Hanley AJ, Sermer M, et al. 2012. Associations of prenatal metabolic abnormalities with insulin and adiponectin concentrations in human milk. Am J Clin Nutr. 95: 867-874.

4. Woo JG, Guerrero ML, Altaye M. et al. 2009. Human milk adiponectin is associated with infant growth in two independent cohorts. Breastfeed Med. 4: 101-109

A version of this post appeared in the May Issue of SPALSH: Milk Science Update. Check out the other columns by awesome colleagues that discuss epigenetic programming, oligosaccharides, and proteins!