Males born to women with obesity mothers are more likely to be overweight at birth and to develop metabolic complications in later life, including liver disease and diabetes. The way male sex hormones activate pathways in the developing liver is partly to blame.
This is the finding of a new study by researchers at the University of South Australia (UniSA) examining the impact of maternal obesity on androgen signaling in the fetal liver.
The results of research were published in the journal Life Sciences.
Maternal obesity: what risks does the unborn child run?
Male fetuses of pregnant women with obesity have different signals that are activated by male sex hormones in the liver, which encourage them to prioritize growth at the expense of their health.
UniSA researcher Dr Ashley Meakin says androgens give men their masculine characteristics and are crucial in their development, but if there are too many of them, male fetuses become too large, causing not only problems at birth, but also affecting liver function as an adult.
Female fetuses exposed to excess testosterone from an obese pregnancy are programmed to deactivate the androgen pathway in the liver, limiting growth and reducing the risks of metabolic disorders in adulthood.
“We know that there are sex differences in metabolic disorders in later life in response to maternal obesity,” says Dr. Meakin.
“Men are more prone to non-alcoholic fatty liver disease and diabetes as adults if their mother with obesity during pregnancy and their birth weight is more than 4 kg.
“They are genetically programmed to prioritize androgens because they support the development of male characteristics, including size, but too much androgens are bad for you.”
The study's lead author, Professor Janna Morrison, head of the Early Origins of Adult Health research group at UniSA, says it is a fine balance for women to get the right nutrition during pregnancy to ensure optimal conditions for the May their unborn child thrive.
“There are also risks of offspring being malnourished during pregnancy,” she says. “If you are too small, too big, born too early, or male, you are more vulnerable to negative outcomes later in life. You need Goldilocks pregnancy: you need to be the right size, born at the right time.”
Professor Morrison says that unless society changes its approach to nutrition, the battle to reduce obesity and its associated health problems will be an uphill battle, from the womb through to adulthood.
“As a society, we must urgently address the problem of obesity. If children were taught the importance of healthy eating early on, this would extend into adulthood, including during pregnancy, where the right diet is so important.”
Dr. Meakin says that in the meantime, supplements that address nutritional imbalances in pregnancy could give the fetus the best chance of optimal development.
This study into androgen signaling in the liver is part of a series of studies by Professor Morrison and colleagues investigating the impact of maternal under- and over-nutrition and obesity on the placenta, heart, lungs and liver.
The article, “Maternal obesity affects androgen signaling in the fetal liver in a sex-specific manner,” is written by researchers at the University of South Australia, the University of Wyoming and the University of Queensland. In this study, tissue samples were obtained from the fetuses of obese pregnant baboons housed at the Texas Biomedical Research Institute in the United States. Cesarean sections were performed at 165 days.
An additional study published in the FASEB Journal identified metabolic perturbations in the liver and skeletal muscle of young non-human primates eating normal diets whose mothers had obesity during pregnancy.
For the study, tissue biopsies were obtained from 19 postpubertal offspring of mothers who were fed a Western diet and who were obese during pregnancy, and from 13 control animals born to nonobese mothers fed a standard diet. All offspring followed a healthy diet after weaning.
The researchers identified 58 significantly altered metabolites in the liver and 46 in the skeletal muscle of children of mothers with obesity during pregnancy, with 8 metabolites shared between both tissues. Several metabolic pathways have been identified from these dysregulated metabolites. These differences in metabolites were not observed in blood samples taken from the animals.
“This study is exciting for two reasons: First, it shows that exposure to an unhealthy environment in the womb has long-term health consequences, and different organs and tissues are affected in different ways.” said corresponding author Michael Olivier, Ph.D., of Wake Forest University School of Me
dicine. “Second, our analysis suggests that it is not possible to simply analyze blood samples to understand what is happening in the liver or muscles.”
Offspring born to mice that exercised during pregnancy were less likely to gain weight after consuming a high-fat diet later in life. Although previous studies have shown that exercise by females with obesity benefits their offspring, this is the first research to demonstrate that the same is true for females without obesity who exercise.
“Based on our findings, we recommend that women, whether they are obese or have diabetes, exercise regularly during pregnancy because this benefits the metabolic health of their children,” said Jun Seok Son, a doctoral student at the Washington State University who conducted the study. study.
Son will present the new findings at the American Physiological Society's annual meeting during the 2019 Experimental Biology Meeting taking place April 6-9 in Orlando, Florida.
The researchers examined the offspring of mice that performed 60 minutes of moderate-intensity exercise each morning during pregnancy. The offspring born to mice that did not exercise were used as a control group.
At weaning, offspring of exercised mice showed increased levels of brown adipose tissue-associated proteins compared to the control group. This type of tissue converts fat and sugar into heat. The researchers also observed higher body temperatures in the exercise group, indicating that their brown adipose tissue was more efficient – or had a higher thermogenic function – which has been shown to prevent obesity and metabolic problems.
After weaning, the babies followed a high-fat diet for eight weeks. The mice in the exercise group not only gained less weight on the high-fat diet, but also showed fewer symptoms of metabolic diseases such as diabetes and fatty liver disease.
“Our data suggest that lack of exercise in healthy women during pregnancy may predispose their children to obesity and associated metabolic diseases, in part through impaired thermogenic function,” Son said.
The researchers intend to carry out further studies to better understand the biological mechanisms responsible for improving metabolic health in children of mothers who exercised.
Exercise during childhood has been shown to promote long-term health and may counteract the risk of developing diabetes from having an obese father.
This is according to research published in The Journal of Physiology. Insulin is a hormone that controls blood sugar levels, and people with low insulin sensitivity do not respond to insulin as normal, which results in increased blood sugar levels. This can lead to type 2 diabetes.
Children of fathers with a high-fat diet or who are obese are more likely to have low insulin sensitivity. This new research indicates that exercise early in life reverses the negative effect of this low insulin sensitivity in adulthood for children and therefore may counteract the risk of diabetes.
The study conducted by Victoria University of Melbourne, in collaboration with the University of Melbourne, involved breeding obese male rats with healthy female rats. Their children underwent physical training for only 4 weeks after weaning and were then assessed as adults in terms of glucose and insulin response, skeletal muscle function, and pancreas structure.
Children of obese fathers had reduced whole-body and skeletal muscle insulin sensitivity and reduced insulin secretion. Early exercise in these children prevented the negative effects in adulthood caused by a high-fat diet in their fathers. It is important to note that early exercise had no positive effects on the pancreas. This was very interesting as the team had previously shown that rats born small for gestational age, like humans, had pancreatic problems as adults but in this case, exercise in the rats' first years of life helped prevented pancreatic problems.
The study is limited because the researchers did not determine at what age changes in an individual's health status begin and when these changes occur. This would help determine the optimal periods during childhood when preventive interventions should be introduced.
The researchers plan to examine which genes are turned on and off to determine the relationship between paternal diet and offspring exercise, as well as how paternal exercise and diet may affect offspring physiology. They also plan to examine whether similar effects occur in larger mammals that have developmental rates more similar to humans.
Dr Filippe Falcão-Tebas, the first author, and Professor Glenn McConell, senior author of the study, commented on the findings: “Obesity due to a high-fat diet in the father may have a negative effect on the offspring's metabolism” . . Our study has shown that physical exercise carried out only in the first years of life of offspring can have long-term beneficial effects on their health by normalizing muscle sensitivity to insulin in adulthood. More work needs to be done, including understanding which genes are turned on and off to cause these changes.”
#Maternal #obesity #male #offspring #health #problems #adults
