Mihai Niculescu, MD, PhD, with the UNC Chapel Hill Nutrition Research Institute, is an expert in the field of epigenetics. He is researching how nutrition influences the genetic interplay between parents and children, specifically looking at omega-3 fatty acid supplementation.
When you make a habit of snacking on fruits and vegetables versus grabbing a hamburger, you may have made a decision that plays a role in determining the health of your children and maybe even your grandchildren.
To some, thinking about the health of family members who are not even born yet may seem far-fetched. Mihai Niculescu, MD, PhD, with the UNC Chapel Hill Nutrition Research Institute (NRI) at the NC Research Campus in Kannapolis, is proving that the nutritional choices parents make today have a measurable genetic impact on the health of future generations.
Environment and Genetics
Niculescu is an expert in the field of epigenetics, the study of how the environment, including nutrition, can influence the activation of our genes. He focuses on nutrition as an epigenetic trigger. He has authored more than 30 peer-reviewed publications, a book and numerous book chapters.
“Environmental effects (can) induce chemical changes on the genes, what we call DNA methylation,” Niculescu explained. “DNA methylation has a profound effect on how genes express. These chemical changes can be inherited through the generations.”
As a physician in his native country of Romania, he became interested in nutrition, and, in 2000, joined a doctoral program at the University of North Carolina at Chapel Hill studying under Steven Zeisel, MD, PhD. Zeisel, now the director of the UNC NRI, is known for his pioneering work with the nutrient choline.
“When we started, there was no word of choline as a supplement,” recalled Niculescu. “We promoted this idea with our studies that choline is an epigenetic factor that counts in brain development and for the overall development of the fetus and then of the baby. Since then, choline has been added to vitamin supplements and baby formula all over the world.”
Omega-3 and Epigenetic Inheritance
Since joining the NRI in 2008, Niculescu carved out a research niche centering on epigenetics, obesity, omega-3 fatty acids and human development. How nutrition influences the genetic interplay between parents and children is one of his primary focal points.
In 2011 and 2013, he published results from a study that examined in a mouse model the effects of omega-3 fatty acid supplementation with flaxseed oil during gestation and lactation (1, 2). The purpose was to observe the brain development of the mouse pups. One finding from the study confirmed that whether or not mouse pups benefitted from their mother’s omega-3 supplementation depended on her omega-3 intake during gestation.
“In order for the supplementation to be efficient in lactation, the mother has to have an adequate intake of the same omega-3 fatty acid during gestation. If the mothers are deficient in gestation, and you suddenly supplement them in lactation it does little to nothing,” Niculescu explained. “Interestingly, flaxseed oil supplementation also induced epigenetic changes to the Fads2 gene (which controls the metabolism of omega-3 fatty acids) in both maternal and pups’ livers.”
Additional findings (manuscript under review) showed epigenetic changes in the pups’ brains in genes that regulate memories and how they are formed and retained. It turned out that flaxseed oil supplementation influenced the expression of memory-related genes such as Arc and Reelin, as well as of genes involved in the epigenetic regulation (such as Dnmt1 and Mecp2). Niculescu emphasized that the findings confirm that “optimizing brain development is a process that happens through different stages of development and is impacted by maternal nutrition.”
In a collaborative study with NRI colleague Carol Cheatham, PhD, who is a developmental cognitive neuroscientist, Niculescu found that mothers who have genetic defects in a gene required for omega-3 metabolism (FADS2), and according to their own DNA methylation, responded to their children’s nutritional needs by giving them more omega-3, even though the children may not need it (manuscript in preparation).
“That will be the first report suggesting that parents impose nutrition on their child based on their own genetics and epigenetics. No one knew that a mother would impose upon the child a nutritional intake as a result of her own genetic and epigenetic background,” Niculescu remarked.
Adult Supplementation with Omega-3 Fatty Acids
Niculescu has looked at the effect of Omega-3 supplementation on adults. In 2010, he and collaborator Diana Tint, MD, of the School of Medicine in Brasov, Romania, conducted a study on omega-3 supplementation with obese adults. The study was conducted in Romania because people do not eat a lot of omega-3, rich fish or take supplements. The study participants who consumed flaxseed oil as an omega-3 supplement stabilized their body mass index (BMI) and maintained blood sugar levels improving their insulin sensitivity. Those who did not receive the supplement continued to gain BMI and experience insulin resistance, a precursor to diabetes.
Obesity is another line of research, specifically finding the answer to why not all individuals who consume high-fat diets become obese. Niculescu and graduate student Daniel Lupu, MD, call this phenomenon obesity resistance.
“We noticed that there are people who are resistant to obesity. No matter how much they eat, they remain lean. What we know is that mice do the same,” Niculescu said. “If you give them a high-fat diet, 30 to 40 percent of the mice remain lean. These mice are genetically identical. So what makes them resistant or sensitive to a high-fat diet? We argue that this is not a genetic issue (but) epigenetic.”
Niculescu and Lupu are working to find markers of DNA methylation that can be measured to see if obesity resistance can be predicted in mice and, eventually, in humans, before the onset of obesity.
“I think this has important implications for preventing human obesity,” Niculescu said. “Do you want to apply a blanket prevention policy where you spend your money on all of the kids, for example, or do you want to focus your spending on preventing those kids who are at risk for obesity? So we are trying to design a mechanism for differentiating individual risk (for obesity).”
Niculescu is confident his research will help to broaden the scope of nutrition research and health policy to consider generational effects. “The goals of my research are to consider interventions that would optimize or improve the health of an individual,” Niculescu said. “We have to go back and take into account inheritance, both genetic and epigenetic. Looking at prevention, we need a policy that is transgenerational.”
For more information, visit www.uncnri.org.
1. Niculescu, M. D., Lupu, D. S., and Craciunescu, C. N. (2011) Maternal alpha-linolenic acid availability during gestation and lactation alters the postnatal hippocampal development in the mouse offspring. Int J Dev Neurosci 29, 795-802
2. Niculescu, M. D., Lupu, D. S., and Craciunescu, C. N. (2013) Perinatal manipulation of alpha-linolenic acid intake induces epigenetic changes in maternal and offspring livers. FASEB J 27, 350-358
3. Tint, D., Anghel, M., Lupu, D. S., Fischer, L. M., and Niculescu, M. D. (2011) Low dose Flaxseed Oil Supplementation Alters the Fatty Acids Profile and the Progression of Metabolic Syndrome in Men without Adequate Medical Treatment. J Nutrition Disorder Ther S7, 1