Kristin Stanford, PhD, Associate Professor, physiology and metabolism at The Ohio State University talks about the effects of exercising while pregnant on breast milk.
What were you and your colleagues looking at in your recent research on exercise and pregnancy and what did you determine?
STANFORD: We had previously shown that in a mouse model of maternal exercise, if the mom exercised before and during pregnancy, it had long-term benefits on their offspring. They had decreased body weight, decreased fat mass and improved glucose metabolism. So, less of a type 2 diabetes phenotype. And those effects were seen throughout their lifespan, about a year of age in a mouse.
Tell me how you did this in mice and how you measured the exercise?
STANFORD: We had the moms on wheel cages. Mice like to run, even when they’re pregnant. A gestation period for a mouse is three weeks. They ran the most the first week of pregnancy. Then, they ran about half that much their second week and then the third week of pregnancy they were moving, but not quite as much. Then, they had their babies. We followed those babies throughout their lifespan over a year.
How did you measure the health of the offspring?
STANFORD: We tracked body weight. We can do this measurement called a DEXA, or a measurement of body composition, where you can determine fat mass. We did that serially, basically every six to 12 weeks. We measured glucose tolerance, which is basically when you give the mouse a bolus of glucose and determine how fast they clear it, and we measured insulin tolerance. We also looked at fasting insulin. Basically, all markers of diabetes.
Were you anticipating those findings?
STANFORD: Previously, what studies had shown in humans and in rodents were that maternal obesity caused detrimental metabolic health later in life, but also that maternal undernutrition caused detrimental metabolic health later in life. So, we weren’t really sure because we always look at exercise as a positive. We were surprised that the undernutrition had these effects to impair health as well and were curious to see what we would find. We were excited because it had been known that maternal exercise has these effects to improve the health of the mom, but also to see how they translated into the health of the offspring.
Does it have to be vigorous exercise? Were these mice very active?
STANFORD: By the time right before they birth, they were running about two kilometers a day. We never track speed or intensity, just actual distance covered in the wheels. So, it was probably a pretty moderate exercise regimen. After doing that, we wanted to determine why this was happening. This kind of brought us to this current project where we want to look to see if exercise affected the breast milk in the moms. We first looked at this in a mouse model, and what we decided to do is take moms that were exercising and moms that were sedentary, and when the pups were born, we swapped the litters. The offspring of the sedentary moms drank the milk from the trained moms, and the offspring from the trained moms drank the milk from the sedentary moms. What we saw is that as those mice aged, the mice that drank the milk from the trained moms had improved metabolic health similar to what we saw in the offspring from moms that exercised. So, they had reduced body weight, reduced fat mass and improved glucose tolerance throughout their lifespan.
So, then this also suggests that there’s something about the breast milk?
STANFORD: Yes. It was exciting for us because it was just the act of drinking the milk that kind of conferred these beneficial effects of maternal exercise. We worked with a collaborator, Lars Bode, who’s at UC San Diego, and sent him milk samples from these moms. He identified this one human milk oligosaccharide, which is called 3’sialyllactose, and is found in both mouse and human milk. It was significantly increased in the moms that exercised, and interestingly was down in moms that were fed a high-fat diet.
What does that protein do?
STANFORD: It’s a human milk oligosaccharide (HMO). This was the first study to identify a role for this oligosaccharide in metabolism. Before this, we knew that it played a role in the immune response, but no one had really determined what it did in terms of metabolic or cardiac health. It’s a sugar. So, women have anywhere up to a hundred and thirty of these HMOs and we’re not really sure why women have diverse populations of milk oligosaccharides. So, that’s why we thought this might be interesting. We knew the HMOs could be regulated by environment, so now we wanted to look to see if they could be regulated by exercise.
Can you play it forward as to what this could potentially do?
STANFORD: One of the exciting things was in collaboration with Aline Andres, from the Arkansas Children’s Nutrition Center, she was running a study in humans correlating activity to breast milk composition. What she was able to do was track women’s steps and activity per day throughout their pregnancy, and then she measured the oligosaccharide content in their milk two months after they gave birth. What we found was that 3’sialyllactose, which is what we saw to be regulated by exercise in mice, was the only HMO that was correlated to steps per day and physical activity in humans. This would suggest that maternal physical activity in humans also increases this oligosaccharide.
What does that do for the baby?
STANFORD: So, in these offspring in a mouse model, we fed this compound back into mice and saw that when we did that, just during their nursing period, we had improved metabolic health. They had decreased body weight, decreased fat mass and improved glucose tolerance throughout their lifespan. They also had preserved cardiac function. More importantly, we also put these mice on a high-fat diet, having fed them 3’sialyllactose during their nursing period protected them from the detrimental effects of a high-fat diet. So, they didn’t become as obese. They had preserved cardiac function and improved glucose tolerance compared to mice that were just fed a high-fat diet.
What does that suggest?
STANFORD: It suggests that this 3’sialyllacose is a compound that really could have a dramatic effect on the health of children. We don’t see these effects at least in a mouse model until they age. One year of age in a mouse could roughly correspond to 45 to 55 in a human. What we’re seeing is that just this act of having this increased 3’sialyllactose during their nursing period has dramatic effects. As we see rates of obesity and Type 2 diabetes and cardiovascular disease increasing rapidly throughout the U.S. and worldwide, this is just one thing that could potentially protect against some of those detrimental effects.
Is there anything you would like to add that you want people to know?
STANFORD: We’re really excited about this data because we see such a tremendous impact on the mice, and then showing that with humans, we do see 3’sialyllacose increase with activity. They weren’t necessarily exercising, but they were moving more, taking more steps per day, and were more physically active. So, I think the hope is that we’ll be able to eventually look to see what the effect is of increasing 3’sialyllactose in humans.
You mentioned that the mice were nursing for a period of three weeks. What does that correlate to? How long would human babies have to nurse to have the same kind of effect?
STANFORD: That’s a great question. I’m not really sure. In mice, that’s just typically when we separate them from their moms. They’re considered young adults at that point. So, that’s kind of the longest that they’re able to nurse. In humans, we’ve only looked at this correlation two months after birth, but I’m not quite sure how long we would see this increase.
Are there next steps for the research?
STANFORD: Yes. What we’d really like to determine is the mechanism through which 3’sialyllactose works. We know that it does work and think that it affects the heart and the liver, but we’re not sure how it’s actually functioning. So, to go back and be able to determine the mechanism of action.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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