Dr Clare M Reynolds, University College Dublin, Ireland
Developmental programming of health and disease (DOHaD) is a hypothesis which examines how environmental exposures before birth, or even conception, and throughout the first two years of life can shape our long-term health outcomes. This hypothesis was originally coined the Barker hypothesis and is based on the work of Professor David Barker (University of Southampton, UK).
In the late 1980s, his examination of historical birth records in the UK demonstrated an association between birthweight and cardiometabolic disease in middle age. The hypothesis has evolved considerably since then and as a result we have a much better idea of how we can improve early life environments to optimise life-long health in the offspring using both human cohort studies and animal experiments.
The role of the parental diet on metabolic inflammation
While researching the role of inflammation on the pathogenesis of insulin resistance and diabetes at University College Dublin, Ireland, I was lucky enough to attend a symposium where Professor Barker was the main speaker. The DOHaD concept was something I had not encountered prior to this symposium and I was fascinated by the role of developmental exposures on obesity and metabolic disease. I shifted my research focus and began studying the relationship between maternal diet and obesity mediated inflammation in the offspring.
In the UK and Ireland up to two-thirds of women of reproductive age are classified as overweight and obese. This is a strong risk factor for cardiometabolic conditions such as hyperglycaemia (high blood sugar), hypertension (high blood pressure), type 2 diabetes and heart disease. There is a clear association between increased fatty tissue and low-grade inflammation. This chronic inflammatory state stimulates molecular pathways which make organs such as the fatty tissue and liver less responsive to insulin. This results in increased glucose and fatty acid concentrations in the blood.
While the metabolic consequences of increased inflammation are well known, there is now emerging evidence to show that reproductive health can also be impacted, which not only leads to complications for women during pregnancy but also to their growing foetuses. These developmental responses can then increase the risk for obesity, cardiometabolic disease and other non-communicable diseases in the offspring. Indeed, many women with pregnancy complications such as gestational diabetes (diabetes that develops for the first-time during pregnancy) and pre-eclampsia have elevated blood levels of inflammatory proteins called cytokines.
Long-term health outcomes It was once thought that these changes were permanent, we now know that when intervention is administered early in life, there is a much greater chance of reversing these negative developmental effects.
Within this context, our lab focuses on two main themes. First, examining the impact of novel dietary determinants that might cause inflammatory changes and impact health during pregnancy, postpartum and in the next generation. Secondly, we are working on determining the efficacy of dietary anti-inflammatory strategies early in life to improve the long-term health of the mother and her offspring who are exposed to either diet-induced or obesity induced low grade inflammation.
Studying early life dietary triggers in rats
Recently our group looked at how artificial sweeteners impact metabolic health during pregnancy in a rodent model. We found that exposure to the artificial sweetener acesulfame-k reduces the mothers’ ability to respond to glucose thereby increasing blood glucose and insulin concentrations and promoting an inflammatory phenotype in the fatty tissue.
This shortens the pregnancy term, reduces the weight of the foetus and causes hypoglycaemia (low blood sugar), all features that resemble gestational diabetes. While the offspring did not have any difference in weight by adulthood, we found that they had increased fat cell size and inflammation in their fatty tissue, which are all early features of metabolic disease.
Our group has also examined an anti-inflammatory lipid called conjugated linoleic acid (CLA) given as a supplement to pregnant rats who had been fed a high fat diet. These high fat diets are rich in saturated fats and promote hyperglycaemia and inflammation during pregnancy which then results in adverse metabolic effects in their offspring.
CLA is found in the beef and dairy produce of cattle fed on grass rather than grain. Pregnant rats that consumed a high fat diet were supplemented with CLA during lactation. In the first experiment we examined the mothers and found that CLA did not reduce weight gain during pregnancy compared to their high fat diet counterparts, but it did improve overall metabolic health by increasing tolerance to glucose and reducing pro-inflammatory proteins in the blood. In the second experiment we examined the offspring and found beneficial health effects throughout the life course despite only being exposed early in life.
The importance of a good quality diet for maternal and child health
Interestingly we found that this occurred in a sex-specific manner where male offspring exposed to a high fat diet had reduced glucose tolerance, hyperinsulinemia (excess levels of insulin) and increased fat cell size and inflammation, all of which were reduced in response to in utero CLA exposure. In contrast the female offspring exposed to a high fat diet had increased blood lipids and increased liver inflammation which was rescued when the mothers were supplemented with CLA.
These findings highlight the importance of good quality maternal diets during pregnancy on both maternal health and long-term offspring outcomes. ‘Environmental Impacts on Pregnancy and Offspring Outcomes: Lessons Learned and Avenues for Intervention’ provides a fantastic opportunity to consolidate the research being done in this area and looks at multiple organ systems and exposures during development, bringing together some of the most exciting research in the field.
Dr Clare Reynolds will be presenting at Environmental Impacts on Pregnancy and Offspring Outcomes: Lessons Learned and Avenues for Intervention on 29 September. There’s still time to register for this exciting one-day conference taking place in London. Save your spot now.