Risk of Obesity Influenced by Changes in Our Genes

Newswise — These changes, known as epigenetic modifications, control the activity of our genes without changing the actual DNA sequence. One of the main epigenetic modifications is DNA methylation, which plays a key role in embryonic development and the formation of different cell types, regulating when and where genes are switched on.

Although DNA methylation was originally thought to be a very stable modification, which once established in early life was then maintained throughout the life span of an individual, there is now growing evidence that the level of DNA methylation can be affected by a range of environmental factors such as parental health, diet and lifestyle.

Researchers from the University of Southampton, as part of the EpiGen Global Consortium, analysed the levels of DNA methylation in umbilical cord tissue of babies born in the Southampton Women’s Survey.

They compared DNA methylation levels present at birth with the amount of fat tissue in the child at four and six years of age. They found that lower DNA methylation at the CDKN2A gene, which regulates the production of fat cells, was associated with a greater risk of the child developing obesity in later life.

Analysis showed that a 10 per cent decrease in methylation at the CDKN2A gene was associated with an increase in fat mass of around 220g, at age four years.

The results, published in EBio Medicine, were replicated in other groups of children and adults, notably the Singapore GUSTO study, the Australian RAINE study and the UK BIOCLAIMS cohort.

Lead author Karen Lillycrop said: “This is exciting new evidence that epigenetic changes detectable at birth are linked to a child’s health as they grow up. It was very promising to see our initial findings confirmed in so many other cohorts. Not only does it strengthen the body of evidence that shows a mother’s health during pregnancy can affect the future health of her child, but it could also allow us to more accurately predict the future risk of obesity. If we can do this, then strategies can be developed in early life to prevent the development of obesity.”

Professor Keith Godfrey, from the Medical Research Council Lifecourse Epidemiology Unit and the National Institute for Health Research Southampton Biomedical Research Centre, and a member of the study team, said: “The new findings provide the first direct evidence linking faltering of a baby’s growth in the womb with epigenetic modifications that themselves may increase the risk of childhood obesity. The findings are now helping us to trial new nutritional interventions before and during pregnancy to reduce the baby’s risk of obesity in childhood and later life, and strengthen the view that effective prevention of childhood obesity has to begin before the baby is born. The findings may also lead to innovative approaches to the treatment of established obesity in later life.”

The EpiGen Global Consortium brings together expertise from the Human Development and Health Academic Unit, MRC Lifecourse Epidemiology Unit and Centre for Biological Sciences, University of Southampton; Singapore Institute for Clinical Sciences; National University of Singapore; Auckland UniServices Limited and the Liggins Institute, University of Auckland. The Consortium’s aim is to improve human health through the life course by further understanding developmental and environmental processes. The research includes a focus on epigenetics, the biology of understanding how gene function is regulated by environmental factors, such as maternal nutrition, during the very early stages of development. This research was carried out as part of a collaboration with the Nestlé Research Centre, in Lausanne, Switzerland.

ENDS

Notes to Editors

The paper entitled ANRIL promoter DNA methylation: a perinatal marker for later adiposity is available from Media Relations upon request
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EpiGen is a global research consortium of leading investigators based at five centres in three countries (Auckland UniServices Limited, University of Southampton, Medical Research Council Lifecourse Epidemiology Unit - University of Southampton, Singapore Institute for Clinical Sciences of the Agency for Science, Technology and Research (A*STAR), and National University of Singapore). EpiGen strives to advance understanding of the developmental and environmental processes that influence health through the life-course. Please visit www.EpiGenGRC.com for further information.
Incepted in 2009 as a collaborative effort with the two major public maternity hospitals in Singapore, National University Health System (NUHS) and the KK Women’s & Children’s Hospital (KKH), GUSTO is the region’s leading longitudinal birth cohort study that combines multi-ethnic Asian participants with detailed records of ante and post-natal data and biological specimens from both mother and child. These data include rare insights into new-born body composition and correlated future obesity via infant MRIs in the 1st week of birth, molecular analysis of birth tissues (placenta, umbilical cord, cord blood) and ongoing breast milk, stool, nasal and buccal swab specimens post-natal up to two years of age for the over 1200 mother-child pairs recruited. Clinical assessments include nutritional, biochemical, imaging, molecular and cognitive studies of the mothers and infants, with extensive implications for understanding future metabolic compromise, allergic and respiratory illnesses, cognitive spectrum childhood disorders and more. Additional information on the GUSTO study is available online at http://gusto.sg.
The Australian RAINE study (Western Australia Pregnancy Cohort) from the Telethon Kids Institute (University of Western Australia) collaborates with the University of Southampton.
Nestlé is the world’s largest food and beverage company. It is present in 189 countries around the world, and its 328,000 employees are committed to Nestlé’s purpose of enhancing quality of life and contributing to a healthier future. Nestlé has one of the most advanced research and development networks in the industry, employing more than 5,000 people, with 40 R&D facilities worldwide.
Other Epigen Global Consortium partners are: Medical Research Council: http://www.mrc.soton.ac.uk/web2/ Auckland UniServices Limited: http://www.uniservices.co.nz/ Agency for Science, Technology and Research (A*STAR): www.a-star.edu.sg Singapore Institute for Clinical Sciences (SICS): www.sics.a-star.edu.sg National University of Singapore: www.nus.edu.sg KK Women's and Children's Hospital (KKH): www.kkh.com.sg National University Health System (NUHS): www.nuhs.edu.sg.