She Saved My Heart… Without Even Knowing It

This is my mom, and she might have saved me from a heart attack. Let's rewind about 30 years to when I was a fetus hanging upside down like a little bat inside my mother's uterus. At that time, she was doing something extraordinary. She was taking care of herself. That simple act of taking care of herself programmed my little body, specifically my little fetal heart, for lifelong health. But why am I talking about this now? Because new research just came out in Nature Cardiovascular Research showing how a mother's diet can program her offspring's heart to be predisposed or protected against cardiovascular disease throughout their lifetime. Whether you're a woman looking to get pregnant, or a guy whose future children's health depends on that of his partner, or just someone interested in developmental biology, epigenetics, and how our choices today ripple into future generations, this is information you should know. So let's talk about how that works, how what a mother eats can program her baby. The choices we make impact our children, but legacy is not fate. Legacy is just susceptibility. You can think of your genome as a vast library, and metabolic health is a relay race. You didn't choose the first handoff, but you're absolutely holding the baton now. Something else is going on here. Now prepare yourself. You might want to sit down for this one because the data are shrinking. So, the paper in question was just published in Nature Cardiovascular Research, and it was primarily conducted in animals, but don't write it off just for that reason. Animal studies are necessary to get a fine mechanistic picture of how this all works. But I do want to emphasize upfront, there is a litany of other data proving that a human mother's health and her nutritional status impact her offspring's chances of developing chronic disease. Obesity, cardiovascular disease, dementia. But if we really want to get into the how, which is important because it also gives us insight into the how not to, we need to move to animal models. So the question, how specifically does a maternal westernized diet high in fat and sugar contribute to their offspring's risk of cardiovascular disease, that remains an open question in the field. So what the researchers did is they fed female mother mice a westernized diet rich in sugar and fat or a control diet during gestation and lactation. They then took the offspring and fed them a control diet for a couple of months before shifting them to a Westernized diet for 8 weeks. Now prepare yourself, you might want to sit down for this one because the data are striking. What you see here is a stain of the aorta, the major vessel coming off the heart, where red indicates areas of plaque accumulation. And what you see is there's clearly far more atherosclerosis, plaque accumulation, in the animals whose mothers ate the westernized diets, even though both groups of offspring ate the same diet, in this case a westernized diet. And it's also interesting to note there were no differences in triglycerides, total cholesterol, HDL, or LDL between groups of offspring based on their mother's diet. So something else is going on here. That question is, what is this something else? So, the researchers then performed gene expression analyses on the endothelial cells, the cells lining the offspring's arteries, to investigate how— again, we're getting into the fine mechanistic details— how the mother's diet might have epigenetically primed the offspring to be more susceptible to atherosclerosis, heart disease. And the researchers found that upon exposure of the offspring to a Westernized diet, there was an increase in expression of genes involved in inflammation and atherosclerosis, like TNF, NLRP3, and CCL3, among the offspring whose mothers consumed the westernized diet. So, the authors summarize it well, I'll quote them: "The maternal westernized diet exposure exhibited a specific role in enhancing the inflammatory response of the offspring when the offspring were exposed to a westernized diet." Now I want to delve deeper into what's actually happening in the offspring as a result of their mother's diet, and that's going to lay the groundwork for solutions. First, consider this: Why are any two cells in your body different? After all, most cells in your body share the same genetic material, so why is an eye cell an eye cell and a heart cell a heart cell? It all comes down to the gene expression patterns, how genes are read or not read into RNA and proteins. This determines a cell's identity function, and fate. You can think of your genome as a vast library. Each cell checks out different books and reads different pages. But some pages are bookmarked, not necessarily read right away, but easier to access when the environment demands, when nutrition demands, and this is where gene-environment interaction comes into play. A mother's westernized diet basically bookmarks specific pages in her offspring's genome, particularly those related to inflammation. And these bookmarks, they don't change the DNA itself, but they make it easier for certain inflammatory genes to be expressed later on when the offspring is also exposed to the inflammatory insult—the westernized diet. So here's how the cascade works in a bit more fine detail. Certain circulating factors in the blood of mothers who consume a westernized diet increase, such as 27-hydroxycholesterol. These bind to estrogen receptors, in particular estrogen receptor alpha, and this activates a transcription factor family called the AP-1 family, including things like Jun and Fos. And these AP-1 transcription factors, they then add biochemical bookmarks to histones, so an acetyl group placed on histones around which DNA is wrapped. And this bookmark primes the genome to be more easily accessible for the inflammatory genes, but only when, and they're only read when, the offspring is later exposed to a westernized diet. So simply put, because I know I threw a lot of $10 words at you, a maternal westernized diet alters signaling in the blood that epigenetically prepares the offspring to mount a more powerful inflammatory response when the offspring are challenged with that same inflammatory insult—the westernized diet—in their life. Now, let's look at another visual: a stain of the arteries from animals grouped by whether or not their mothers ate a westernized diet or control diet, and whether they ate a westernized diet or control diet. The rows represent stains of 3 different inflammatory mediators: TNF, a cytokine, NLRP3, the inflammasome, and CCL3, from top to bottom. The rightmost column shows animals whose mothers ate a Westernized diet and then who also ate a Westernized diet themselves. And the second column from the left shows animals whose mothers ate a Westernized diet, but the offspring, they themselves ate a control diet. Now what should jump out at you is that only in the rightmost column, where the mother and the offspring ate a westernized diet, are these inflammatory markers very strongly expressed. Don't overthink it. Do you see more color? Yes. That's the point. The contrast is stark and meaningful. And the punchline? The choices we make impact our children. This is actually true for males as well. And the choices our parents made they impact us today. There is a legacy of lifestyle, but legacy is not fate. Legacy is just susceptibility, at least when we're talking about epigenetics. So now I want to turn to how to combat your mother's diet. The most obvious solution is simple: irrespective of what your parents ate, you can choose to eat well. This means different things to different people, but if you can, high level, skip processed food and added sugars and instead eat foods that are ingredients themselves rather than foods that have ingredient lists, you're you're going to be better off than the majority of the population. But if you really want to be metabolically elitist and take this one step further, we can ask the question: what diets or metabolic states might turn off the genes or signaling pathways that were primed by a maternal westernized diet? And there is an answer to that question: ketogenic diets and ketosis— very low-carb diets that induce this metabolic state of ketosis. Interestingly, ketogenic diets and ketosis have been shown to reduce TNF levels, inhibit the NLRP3 inflammasome, and lower CCL3 expression. So fighting the three expression patterns that we saw in this study. Coincidence? Unlikely. A ketogenic state is generally anti-inflammatory in nature, so it makes high-level sense that it would oppose the epigenetic priming caused by an inflammatory lifestyle, in this case a high-fat, high-sugar westernized diet eaten by our mothers. So, does this mean that if your mother ate a westernized diet while she was pregnant, you need to eat a ketogenic diet? No, not necessarily. And I doubt we'll ever see a randomized controlled trial testing whether cardiovascular benefits of ketosis are greater in people whose mothers ate a high-fat high-sugar westernized diet. That study will just never be done. But I still think these data are food for thought. Unprocessed food for thought at that. Well, I guess I processed them a little bit for you. Oops. Anyway, the takeaway is epigenetic legacy is not destiny. We inherit much more than just eye color and bone structure from our parents. We inherit biological momentum. But momentum can be redirected and shifted. Yes, your mother's diet may have epigenetically shaped how your body responds to a modern westernized food environment, but the decisions you make now still matter, possibly even more than ever. This is not fatalism. This is informed empowerment. The same molecular doors that were propped open by a prior generation can in theory be shut, or at least kept from swinging wide open by the next. So if this study reveals anything, it's that metabolic health is a relay race. You didn't choose the first handoff, but you're absolutely holding the baton now. That's pretty powerful. So choose wisely. Your future and maybe your kids' future depends on it.