Mom's Prenatal Smoking Epigenetically Linked to Offspring's Obesity

November 26, 2018
Mom's Prenatal Smoking Epigenetically Linked to Offspring's Obesity
Source: Lothar-Shulz/Getty Images

It is well recognized that mothers who smoke during pregnancy increase the risk that their babies will be born premature and have a low birthweight. More recent research has found that exposing the fetus to tobacco smoke also increases the risk of pediatric and adult offspring obesity, but the mechanisms responsible for this aren’t really understood.

Studies by a University of Kentucky-led team now suggest that maternal smoking increases levels of a protein called chemerin—which is linked with obesity in adults—in their newborn babies. The findings, reported by Kevin Pearson, Ph.D., and colleagues in Experimental Physiology, suggest that smoking during pregnancy may impact on epigenetic control of chemerin in the fetus and newborn, which then increases the risk of obesity later in life. Describing the studies in a paper titled, “Smoking during pregnancy increases chemerin expression in neonatal tissue”, the researchers concluded, “Our data provide a potentially novel mechanism behind increased later-life obesity risk in babies born to mothers who smoke during pregnancy.”

In the U.K., 26% of adults and 20% of children are obese, which costs society an estimated £27 billion a year, according to U.K. government figures cited by the Physiological Society. The rates of obesity also continue to rise, which suggests that environmental factors other than diet exercise and genetics may be contributing. In the U.S., nearly 35% of adults and 20% of children aged 6–19 years are obese, which costs the U.S. healthcare system some $200 billion annually, the authors added. “Though multiple factors play a part in the development of obesity and metabolic disorders, one potential contribution is the in utero environment during pregnancy.”

Chemerin is an adipokine that regulates fat cell differentiation. Levels of the chemokine are elevated in people who are obese and those exposed to smoke, but whether levels of chemerin are altered in neonates exposed to cigarette smoke in utero hasn’t been investigated, the authors wrote. They examined chemerin gene expression discarded foreskin samples from circumcised babies of mothers who smoked during pregnancy, compared with newborn babies from non-smoking mothers. Foreskin is simple to collect, and the team had previously shown that it has similar properties to tissues such as fat, which it wouldn’t have been possible to collect from the newborns.

Tissue analyses showed that chemerin expression was significantly higher in the foreskin tissues of babies that had been exposed to cigarettes smoke in utero, compared with controls. “Cells that were collected from babies born to smokers demonstrated elevated chemerin mRNA expression compared to those cells isolated from babies born to non-smokers,” the researches wrote. Chemerin levels were also increased in smoke-exposed foreskin-derived primary dermal fibroblasts that were grown in culture and stimulated using an adipogenic cocktail.

Interestingly, further analyses showed that chemerin DNA methylation was lower in the whole tissues of newborns born to smoking mothers, suggesting that epigenetic mechanisms may be involved in smoke-induced changes to chemerin gene expression. “The present data support a potential mechanism whereby children or adults exposed in utero to cigarette smoke could demonstrate greater rates of obesity later in life,” the team concluded. “Others have shown that although newborns exposed in utero to cigarette smoke tend to be smaller, they do have greater rates of obesity later in life suggesting altered developmental programming …”

The team acknowledged that their study does have limitations, not least because the results can’t be extrapolated to female offspring. Moreover, the researchers write, “…we are making these measures in epidermal/dermal samples and predict that the adipose tissue would respond in a similar fashion which may not be the case. Due to limited tissue availability, we were only able to assess DNA methylation and mRNA expression of chemerin rather than protein expression in our samples so this should be investigated in the future.” Nevertheless, they commented, “Despite the present limitations, these results provide important new evidence for a link between maternal smoking during pregnancy and increased chemerin mRNA expression.”

The team aims to evaluate the effects of other maternal behaviors on offspring health. “Our long-term plan is to study the impact of exercise during pregnancy and its ability to improve health outcomes in offspring,” Dr. Pearson stated. “However, as we began to transition our work from laboratory animals to humans, it quickly became apparent that a fairly high percentage of the pregnant population delivering at our hospital continued to smoke cigarettes throughout pregnancy. Thus, we set out to investigate the mechanisms of why babies born to smokers are at risk for later diseases. In the future, we would love to work on ways to improve smoking cessation programs or ways that we can increase exercise levels in smokers as a way to combat the negative outcomes in offspring, but we are really just starting to scratch the surface in this area.”