Parental exercise may protect children from obesity

The finding comes from studies with mice and was presented at the 30th Annual Meeting of the Brazilian Federation of Experimental Biology Societies.

By Karina Toledo

Agência FAPESP – Babies born to women who exercise regularly before and during pregnancy and to fathers who keep fit prior to a child’s conception are less likely to be obese when they grow up.

This is the main finding of a study in mice performed at the Federal University of São Paulo (UNIFESP) in Brazil. The principal investigator was Professor Ronaldo de Carvalho Araújo, and the research was supported by FAPESP. Preliminary results were presented on September 10 at the 30th Annual Meeting of the Brazilian Federation of Experimental Biology Societies (FeSBE), held at the University of São Paulo’s Medical School (FM-USP).

“The results suggest that the offspring of mothers and fathers submitted to the treatment become less obese than the children of sedentary parents when fed a high-fat diet. Several factors appear to reduce food intake and increase energy expenditure,” Araújo told Agência FAPESP.

The study was conducted as part of Frederick Wasinski’s and Rogério de Oliveira Batista’s PhD research. Aline Midori Arakaki, a master’s student, also collaborated.

The first experiment evaluated the effects of maternal exercise on descendants. Female mice were trained to swim for an hour per day, five days per week, for four weeks, with a load corresponding to 3% of body weight attached to the tail. After this period, they were mated. Training continued with the same intensity during gestation.

“We used this protocol because previous studies had already demonstrated its effectiveness in improving cardiovascular performance in mice,” Araújo said.

At the end of gestation, the scientists observed that the body weights of trained females were similar to those of the control group mice, which had remained sedentary throughout gestation. However, the percentage of fat in trained mothers was approximately 20% lower. The number of pups born to both groups was also similar.

The weight of the pups at birth was 7% lower on average for the group of trained mice and below the weight considered normal. “This is a significant difference, bearing in mind that a litter may comprise between five and ten descendants,” Araújo said.

The analysis of placenta showed decreased expression of a gene associated with energy metabolism and responsible for the production of leptin, an appetite-inhibiting protein, in trained mothers. It also showed reduced expression of placental growth factor (PLGF), a protein that plays a critical role in forming new blood vessels.

“These findings suggest that the offspring of trained mice received a smaller amount of nutrients during gestation, which would explain their lower birth weight,” Araújo said. “Part of the energy that should have gone to the pups may have been used by the mothers to keep swimming. However, we’re analyzing the data further to be sure. Among other factors, we’re looking at the number and the size of blood vessels to determine the extent to which placenta is affected by physical exercise.”

A comparison of adiponectin and leptin levels in females’ fatty tissue showed no significant differences between the two groups. However, trained mothers displayed higher levels of blood corticosterone, the rodent hormone equivalent to cortisol in humans, suggesting they had not adapted well to the exercise.

Resistance to obesity

Low birth weight is generally associated in the scientific literature with higher risks of obesity, insulin resistance, diabetes and cardiovascular disease in adulthood.

According to a theory known as “fetal programming”, nutritional deprivation in the mother during gestation forces the fetal organism to adapt to this adverse intrauterine environment. Gene expression is reprogrammed so that the baby’s metabolism focuses on saving energy. This reprogramming continues after birth and can contribute to weight gain if the pattern of calorie intake improves.

Some studies suggest that administering synthetic corticosterone to pregnant animals can induce an effect similar to nutritional deprivation. Stress during gestation may thus lead to low birth weight and therefore a higher risk of metabolic and neurological diseases.

However, the results of the experiments performed at UNIFESP were diametrically opposed to those expected according to the logic of fetal programming. Pups with a low birth weight displayed higher resistance to obesity and insulin sensitivity than did normal birth weight pups.

When the offspring of both groups reached adulthood, i.e., three months of age, they displayed equivalent weights and sizes, and they were fed a high-fat diet for 16 weeks. After this period, the offspring of sedentary females weighed 60% more on average than at the start of the experiment. No weight alterations were observed in the offspring of trained mice. This group consumed less food during the 16-week period, and the basal caloric expenditure of the group was approximately 5% higher than that of the control group.

Although basal blood sugar was similar for both groups, when the researchers administered synthetic insulin to the animals, they found that the offspring of trained mothers were able to capture sugar more quickly, pointing to greater insulin sensitivity.

“We don’t know for sure whether this change was related to maternal exercise,” Araújo said. “They may have been more sensitive to insulin because they didn’t put on weight.”

When the researchers analyzed hormones associated with hunger control, they found that the offspring of trained females had higher levels of PYY, a peptide secreted into the blood by cells lining the lower small intestine soon after eating to reduce appetite. They also observed an increase in the cytokine interleukin-6 (IL6), the production of which is stimulated by exercise training. However, there were no alterations in leptin or insulin.

“It’s probable that several mechanisms are talking to each other and that this interaction results in diminished appetite and increased caloric expenditure, so that the baby mouse is protected against obesity,” Araújo said.

Paternal influence

The group decided to next investigate whether paternal exercise also affected the metabolism of newborn mice. To their surprise, the researchers found very similar results to those of the experiment with females.

As in the previous case, the males were subjected to the swimming protocol with a tail load for four weeks and were then mated. A lower level of corticosterone was observed in the trained group than in the control group.

The offspring of trained fathers, albeit gestated by sedentary mothers, were also born with low weight and remained smaller than the control group offspring until adulthood. When challenged with a high-fat diet at three months of age, they did not gain weight. They ate less and expended more energy. Insulin sensitivity was not measured.

According to Araújo, recent research suggests that obese parents tend to have obese children, owing not only to shared bad eating habits but also to inherited alterations in gene expression patterns.

“These are known as epigenetic alterations,” he said. “They include the methylation of DNA, the addition of methyl radicals to specific DNA regions, and the modification of histones, which are proteins that regulate DNA packing: these alterations can be passed on to descendants via sperm. So far, no research has shown that epigenetic alterations induced by physical exercise in a father can also be transmitted to offspring, but we believe that this was what happened in our experiment.”

The next step is to compare semen from trained and untrained males to see whether there are differences in sperm count and sperm motility.

“We also plan to use gene sequencing techniques to compare the extent and sites of DNA methylation in each group and to detect differences in the miRNA expression pattern,” Araújo said. A microRNA (abbreviated miRNA) is a small non-coding RNA molecule that regulates the expression of protein-encoding genes.

Another future project aims to evaluate the grandchildren of trained mothers and fathers to assess whether the resistance to obesity found in offspring is transmitted to the second generation, which would support the epigenetic modification hypothesis.

According to Araújo, additional analysis is required to confirm that physical activity in parents can induce protective and beneficial fetal programming. He also argued that it is too soon to transpose the results observed in mice to humans.

“It’s worth recalling that the American Academy of Obstetrics & Gynecology currently recommends moderate exercise for pregnant women,” he said. “The recommended intensity is much lower than that in our experiment.”