Blocking an inter-generational cycle of obesity

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Being exposed to high levels of nutrition before birth can influence the development of networks within the brain that regulate appetite to permanently set a pattern of appetite for life, according to researchers from the University of South Australia.

In addition to changing the way in which the brain develops, high levels of nutrition before birth stimulate the developing fat cells, making them more likely to increase in size, resulting in obese babies who stay obese throughout their lives.

How babies respond to nutrition from their mothers before birth and how the nutritional environment before birth impacts on health after birth has been the focus of a major research program being undertaken by UniSA’s Pro Vice Chancellor: Research and Innovation, Professor Caroline McMillen.

“Babies born with a high birth weight have an increased risk in later life of obesity and associated health risks including diabetes,” Prof McMillen said.

“More women are entering pregnancy with a high body mass index and a range of studies worldwide have shown that heavier mothers generally have heavier babies who grow up to be heavier adults with resultant health risks. There is currently a real concern that the programming of obesity from before birth will result in an inter-generational cycle of obesity,” Professor McMillen said.

What is clear and what hasn’t been dealt with effectively to this point is that obesity is established very early in life, according to postdoctoral research fellow, Beverly Muhlhausler from UniSA’s Early Origins of Adult Health laboratory.

“We need to stop infants from becoming obese in the first place,” Muhlhausler said.

“Understanding what happens early on can help to define the critical window in which to introduce an intervention that will block the obesity cycle. We know that window of opportunity is small and we know that we have to intervene very early in development to have a lasting effect.

“Evidence from our work suggests that the neural network, the pathway that regulates appetite and food choices in the brain, is more flexible or ‘plastic’ as it develops before birth and for a short time after birth but once the neural connection is set up, the appetite regulation pattern becomes permanently set,” Muhlhausler said.

The researchers believe that the same early setup applies to genes within the fat cells, which regulate how much fat is made in response to particular stimuli such as a meal or high glucose.

“Having an understanding of the response mechanisms that are set early in life will help us to intervene early in the neonatal period and potentially prevent childhood obesity,” Muhlhausler said.

The research by Prof McMillen and Muhlhausler has been given a boost with funding from a National Health and Medical Research Council project grant to look at the early origins of obesity. Their research will focus on intervening to block the effects of over nutrition by administering a specific drug that can stop a particular gene inside fat cells from being over activated and producing too much fat tissue.

“We’ve shown that this gene is switched on too early in an environment of high nutrition. If we can block this gene early, we can cut the obesity rate in the offspring of obese mothers and the inter-generational cycle of obesity will be broken. Understanding the response mechanisms that are set up early in life will help us to move forward,” Muhlhausler said.

“While we know that over nutrition before birth makes obesity harder to reverse, watching too much television, lack of exercise and eating junk food will still make people fat. Healthy food choices and moderate activity levels are very important for everyone, regardless of their beginnings.”

Researchers in the Early Origins of Adult Health laboratory, based within UniSA’s Sansom Institute, have won three National Health and Medical Research Council (NHMRC) project grants worth more than $1 million to look at how events before birth (changes in nutrition around conception, and too much or not enough nutrition) can have an impact on adult health.

In addition to the early origins of obesity, Prof McMillen is conducting studies with National Heart Foundation Research Fellow Dr Janna Morrison on how the heart functions in low birth weight babies (less than 2.5 kilograms) and why small babies have a twofold risk of developing cardiovascular disease when compared with normal birth weight babies.

Dr Morrison is also undertaking research with Dr Giuseppe Posterino on under nutrition caused by dieting around the time of conception, which causes changes in development before birth that could be related to changes in adult health.

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