Excess weight could contribute to increased inflammation during pregnancy

Study evaluates inflammatory markers in blood samples obtained from pregnant women and reveals changes in the levels of peptides secreted through adipose tissue associated with body mass index.

By Karina Toledo

Agência FAPESP – During pregnancy, obese and overweight women have higher risks of developing complications such as preeclampsia and gestational diabetes. A recently concluded study at the Universidade Federal de São Paulo (Unifesp), funded by FAPESP, offers new clues that can help elucidate why this occurs.

Through the analysis of blood samples obtained from almost 200 pregnant women, the researchers concluded that excess weight is associated with significant alterations in the levels of two substances secreted through the adipose tissue, as well as leptin, and these alterations can contribute to an increase in systemic inflammation.

“During pregnancy, there is a degree of physiological inflammation resulting from the mother-fetus interaction. In addition, obesity, diabetes and hypertension are diseases with a strong inflammatory component. Therefore, evaluating the combination of gestation and obesity with a focus on inflammation seems important for understanding the risk and mechanisms involved in these obstetric pathologies,” said Silvia Daher, coordinator of the Laboratory of Obstetric and Experimental Physiology at Unifesp.

The blood sampling was conducted in the third trimester of gestation because, according to Daher, gestational diabetes is a disease that generally only manifests in the second half of pregnancy. Based on the pre-gestational body mass index (BMI), the volunteers were split into four different groups: individuals with healthy excess weight (BMI equal to or greater than 25), individuals with excess weight and gestational diabetes, healthy individuals with ideal weights (BMIs between 18.5% and 24.9%) and individuals with an ideal weight who have gestational diabetes.
“We grouped the individuals as such so that we could precisely verify whether the alterations were associated with diabetes or were in fact the result of being overweight,” said Daher.

Three different parameters for measuring the degree of systemic inflammation were analyzed in blood samples. The first step was to measure the serum levels of three different cytokines: tumor necrosis factor alpha (TNF-α) and interleukins (ILs) 6 and 10. These cytokines are molecules produced by cells of the immune system and have an important role in modulating the inflammatory response that functions to combat infections. 

“In the case of IL10, which has anti-inflammatory action, we noted associated declines solely in diabetes; however, there was no difference related to excess weight. Regarding IL6 and TNF-α, which are pro-inflammatory cytokines, we did not notice significant differences between the groups,” explained Daher.

The second parameter evaluated was the presence of active immune cells in the blood of volunteers. Among these immune cells are natural killer cells (NK) and CD8+ T cells, which are two types of lymphocytes capable of releasing toxic substances to kill, for example, tumor or virus-infected cells.

“At this stage of pregnancy, these defense cells have been diminished because they may be aggressive toward the fetus. We verified greater activation of lymphocytes related to diabetes, but not the IMC,” said Daher.

Finally, the blood samples were examined to determine the levels of adipokines, which are peptides secreted by adipose cells with several functions including regulation of the immune response.

“Adiponectin is an adipokine with anti-inflammatory and anti-hyperglycemic action. Normally, it diminishes during gestation because the glucose circulating in the body must increase to fulfill the needs of the fetus. Leptin and resistin are adipokines that induce production of inflammatory cytokines, such as IL6 and TNF-α, possibily worsening the insulin resistance typical of gestation and increasing systemic inflammation,” explained Daher.

The analyses show a significant reduction in the levels of adiponectin associated with excess weight as well as a reduction in the leptin level. “It is a factor that could be contributing to inflammation and to greater insulin resistance in overweight pregnant women,” stated Daher.

Obesity and metabolic disturbances

According to Daher, the fact that the results show alterations in immune cells and cytokines associated solely with diabetes and not BMI may be due to the small number of obese individuals in the sample.

“We now intend to study a group of women with a BMI greater than or equal to 30 to determine whether there are more intense alterations in these and other inflammatory markers,” she explained.

The growing epidemic of obesity worldwide, stressed Daher, also affects women of reproductive age. The literature indicates that obese pregnant women have a four-fold greater risk of developing gestational diabetes, and their chance of developing preeclampsia is doubled.

“Anyone suffering from gestational diabetes has an increased risk of having type 2 diabetes in the future, and the child is also more prone to metabolic disturbances. The same occurs in preeclampsia. It is a risk for both the current and future generations,” said Daher.

Some of the data obtained during this study as well as data from previous FAPESP-funded studies performed by this group were released in two reviews published in the American Journal of Reproductive Immunology and the Journal of Reproductive Immunology.

Currently, the team is evaluating the lipidic profile of overweight pregnant women to discover how alterations in the cholesterol level are related to the inflammatory markers studied.

“We are also investigating some of the genetic polymorphisms to determine, for example, whether someone could be genetically disposed to produce greater levels of adiponectin or lower levels of leptin. This will help us to understand why some of the people with excess weight get sick while others do not,” explained Daher.