I had recently planned to work on a blog post focusing on childhood obesity and the discussion of healthy eating and exercise. As I sat there trying to type new, creative ideas based on the already known mantras of Eat Your Veggies, Exercise 60 Minutes a Day, Don’t Snack at Night, Drink Your Water, etc, I found myself frustrated. It didn’t feel like I was bringing anything new to the table. That was when I remembered a discussion I had with my dad about epigenetics and childhood obesity. As an OBGYN and overall scientific knowledge enthusiast, my dad had reviewed many journal articles on how epigenetics affects our predisposition to obesity and other comorbidities. He even developed a lecture on it and was kind enough to send it to me so we could discuss it further. Upon this recollection, I recognized that this topic needs more discussion and exposure. What if I told you that a dad’s exercise and eating habits could affect his child’s risk for obesity later in life, even before conception? Sound interesting? Then read on, but be warned. The information below is just the tip of the iceberg when it comes to epigenetics. There is still little we understand about it and new research continues to be released.
The first question you may have is “What is epigenetics?” It is possible you have heard the term in the main stream media or a passing article but never actually looked into it. When you examine our DNA you can find varying types of genes present in different people. Epigenetics is not the act of changing our DNA; it is the manipulation of the genes present to either express them more often or shut them down. This is done through various mechanisms including methylation, microRNA expression, and histone modification. I won’t bore you with the specifics of how these changes occur on the microscopic level. However, it is important to know that DNA methylation is one of the key factors in epigenetic changes in the body. This is due to the changes being very stable during the replication of cells, increasing the chance that these changes in gene expression may be passed down to our offspring.
So how does epigenetics affect obesity in humans? First, we need data. As I mentioned above, I started out with the information my dad had already collected. To dive further into this, I also utilized a 170 page document titled “Examining a Developmental Approach to Childhood Obesity: The Fetal and Early Childhood Years: Workshop Summary.” This was authored by Leslie A Pray, who was part of the Food and Nutrition Board at the Institute of Medicine. Utilizing this plethora of information, I feel I can present a quick summary of information to better understand how epigenetics can affect obesity in kids.
Science typically refers to animal models first. This is due to the fact that many animals share a large amount of their DNA with humans. There is evidence that when mammals such as mice are cloned for the purpose of clinical studies, the cloned animals typically are heavier with adult onset obesity. Nothing has changed in the DNA sequencing of the mouse, but outside factors have affected the way these genes are expressed.
One famous study in regards to epigenetics involves the Agouti mouse. Were you confused when the image for this blog post had two different looking mice? Those are the Agouti mice. The fascinating thing about these mice is that they share the exact same DNA. They looked the exact same at birth. However, one remained dark, furry, and lean while the other developed yellow fur and obesity. What was found was that methylation patterns at the Agouti viable yellow locus (also called the Avy locus) greatly affected the varying mice phenotypes. The darker, leaner mouse had more methylation at this gene locus, while the yellow, heavier mouse had very few methylation inclusions. This methylation pattern affected how the genes at the Avy locus were expressed, leading to very different clinical outcomes in the otherwise genomic identical creatures.
Moving from our four-legged friends to the bipedal world, one can see how this effect of epigenetics could greatly influence gene expression of the human genome. One example is looking at cases of famine during World War II. During 1944-1945 food supplies were blocked by the Nazi army into Dutch territory while laying siege to Leningrad. Children born during this time were small for gestational age, most likely due to poor nutrition while in utero. However, once the famine diminished and food sources increased in the region, these children had a greater risk of obesity, cardiovascular disease, and type II diabetes compared to children born shortly after them within the same region. This potentially indicates that while in utero a specific gene controlling things like hunger drive, metabolism, or other factors may have been altered via epigenetic factors, preparing the unborn fetus for future famines once born into the outside world. Yet, their nutrient rich diets in early childhood did not match the body’s gene expression, thus leading to higher rates of obesity and other comorbidities. Studies looking at similar children in Russia around the same time did NOT show this increase in obesity or other health complications due to the fact that they continued to experience episodes of famine in post WWII USSR.
Maternal glucose control, maternal weight gain, or variations in over- or under-abundance of food during pregnancy can have an increased influence on childhood obesity. There have also been studies showing that the methylation pattern of certain genes in cord blood samples of newborns correlate to childhood obesity. Obviously, many factors may affect how genes are expressed or quieted secondary to factors during pregnancy. What if I told you that things you do BEFORE you conceive a child can also influence their risks for obesity? Are you appropriately freaked out yet?
Let’s look at dads for a moment. Normally when people see a dad’s role in the conception of a child, we are little more than sperm donation. Sorry. I said it. They don’t see the father’s health as a contributing factor to the child’s future health. Moms tend to get a lot of the blame. However, the sperm’s role in childhood development is HUGE. I won’t get into all the science behind sperm formation, sperm RNA, etc. There are plenty of studies that show that paternal health can greatly affect their child’s health AS WELL as their GRANDCHILDREN’S health. Crazy, right?
One commonly cited study is the Overkalix study done by Kaati et al in 2002. This study followed a series of Swedish citizens born in 1890, 1905, and 1920. They followed the offspring and their offspring until 1995. The purpose of the study was to assess if the abundance of food during a father’s slow growth period (before the prepubertal peak) affected his child’s risk of obesity as well as his grandchild’s risk. The results were impressive. Those exposed to a limited amount of food during this slow growth period had offspring with a reduced risk of cardiovascular disease. Those exposed to an abundance of food during this period had GRANDCHILDREN with increased risk for diabetes.
More recent mouse model studies performed by Carone et al in 2010, Fullston et al in 2013, and Lambrot et al in 2013, further demonstrated the importance of paternal nutrition on the health of future generations. These studies demonstrated that male mice who were fed high-fat, low-protein diets led to offspring with a higher fatty liver composition. They also showed that paternal mice fed diets to induce obesity had offspring who also had offspring (grandchildren) with increase adiposity at birth. In other words, their fat content was higher compared to muscle content at birth, increasing the risk of obesity later in life. What was interesting was that the female children of the obese dad had a higher risk for this than the male offspring, yet the male grandchildren had a higher risk for adiposity than the female grandchildren. They were even able to isolate the microRNA associated with the sperm that possibly caused these outcomes. Considering my maternal grandfather is still alive, active, and in a good state-of-mind at 103 years old, I am hoping some of that got passed down to me.
As mentioned above, maternal influences can affect childhood obesity risks. There is evidence on how maternal BMI can directly affect methylation within the mom’s genetic structure. Most studies seem to indicate that methylation does NOT affect BMI, rather that BMI affects methylation. So if you can manage your health and reach a healthier BMI, you can most likely affect the amount of methylation one passes on to their offspring.
Some animal and human studies have also targeted leptin as a contributing factor to childhood obesity. Increased exposure to leptin in utero has shown an increase in early weight gain as well as changes to the hypothalamus, which is a prime center in our brain that affects our hunger and satiety signals. The levels of leptin in offspring may also be partially affected by maternal glucose control during pregnancy.
Many of you may be reading this and thinking to yourself that all is lost and no amount of diet and exercise could possibly help these epigenetic changes in yourself or your children. Right? Wrong. Nutrition is a prime environmental factor that can both positively and negatively affect our gene expression when altered during our prenatal, neonatal, and pubertal periods of life. Other studies have shown that by simply adding exercise to a parent’s routine, the negative outcomes from poor diet can be neutralized. Although we can’t change how our grandparents ate during the Great Depression which may have affected our genetic expression now, we CAN influence our current dietary and exercise habits in order to influence our kids and their kids.
So, what can we do? Knowing that maternal weight gain during pregnancy as well as glucose control affects childhood obesity risk, a mom can still manage her eating and exercise habits during pregnancy to improve these outcomes. Appropriate weight gain AFTER the first trimester tends to be about a pound per week (this was edited as I accidently typed during the first trimester in the first edition). Too much weight gain in the first trimester can have negative effects. Developing gestational diabetes during pregnancy also does not automatically lead to negative epigenetic factors for the unborn infant. Appropriate glucose control managed through healthy eating, exercise, and possibly medications can improve the fluctuations of glucose levels as well as leptin in the fetus during this vital stage of creation.
Dads, it is really quite simple for us. Well, maybe not that easy. Be healthy. Seriously. Take care of your diet. Get your exercise. Do this on a regular basis. We never know WHEN we will conceive a child, and since our sperm is constantly turning over it is important to have the least amount of negative epigenetic factors present when it does happen.
Epigenetics is still considered a young field. There is a lot of information out there we still don’t understand or know how to manipulate to get the positive results we desire. What we do know is that the healthier we are as parents, the healthier are kids tend to be. Teach your kids to eat healthy at a young age. Keep them active. Stay active yourself. The information above is just a small amount of the data available involving epigenetics and the human genome. Other factors like toxic stress, environmental factors, placental changes, and further influences can both positively or negatively express our genomic expression.
On a side note, the message above is not meant to force us into unhealthy eating in terms of restricting our diet or calories. Undernutrition can be just as bad as overeating, so make sure to get all the nutrients your body needs in a healthy way.
Remember – none of us are perfect when it comes to our eating or exercise habits. If you remember to do just a little better every day, it could mean a huge difference in the way our bodies express various genes to allow us to lead longer, healthier, happier lives.
Embrace the Imperfect.
Imperfect Dad, MD