Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

International Journal of Obesity (2011) 35, 883–890 & 2011 Macmillan Publishers Limited All rights reserved 0307-0565/11 www.nature.com/ijo PEDIATRIC REVIEW Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions K Rooney1,2 and SE Ozanne3 1 Discipline of Exercise and Sport Science, Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia; 2Boden Institute, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia and 3Department of Clinical Biochemistry, Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK Obesity now represents one of the major health care issues of the 21st century. Its prevalence has increased exponentially in both the developed and developing world during the last couple of decades. Such a rapid rise can therefore not be explained by a change in genotype, but must result from environmental factors and their interaction with our genes. There is clear evidence to show that current environmental factors such as current diet and level of physical activity can influence our risk of obesity. However, there is growing evidence to suggest that factors acting during very early life can influence long-term energy balance. One such factor that is emerging as an important player is maternal obesity and/or over-nutrition during pregnancy and lactation. Early life may therefore represent a critical period during which intervention strategies could be developed to reduce the prevalence of obesity. International Journal of Obesity (2011) 35, 883–890; doi:10.1038/ijo.2011.96; published online 17 May 2011 Keywords: developmental programming; maternal obesity; insulin resistance; maternal diet Introduction Childhood obesity is a global public health problem. The international obesity task force have reported that 1 in 10 children (B155 million) aged between 5 and 17 years are overweight.1 In 2005, the World Health Organisation reported that at least 20 million children under the age of 5 were overweight.2 That prevalence has doubled to an estimated 42 million in 2010.3 Of particular concern is the risk of childhood obesity developing into obesity in adolescence and adulthood. A central dogma to obesity development focuses on the individual environment such that obesity is a lifestyle choice resulting from an energy imbalance. Principally, caloric intake exceeds caloric expenditure. However, strong relationships between parental body mass index (BMI) and offspring BMI,4 as well as the identification of familial risk factors for obesity,5 are suggestive of genetic factors contributing to obesity development.6 It is therefore more likely that neither environ- Correspondence: Dr S Ozanne, Department of Clinical Biochemistry, Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke’s Hospital, Level 4, Box 289, Cambridge CB2 0QQ, UK. E-mail: Received 16 December 2010; revised 31 March 2011; accepted 4 April 2011; published online 17 May 2011 ment nor genes are acting alone and that gene–environment interactions resulting in epigenetic modifications of the genome are driving the rapid increased prevalence of obesity. Of interest to the current review, is the potential predisposition of the core behaviours underlying obesity development arising from environmental exposures experienced in utero or early postnatal life. Overeating and reduced physical activity have been identified in offspring of obese mothers. Evidence from animal studies supports the hypothesis that this results from the obesogenic environment experienced in utero rather than pure genetic factors. The precise obesogenic environmental factors that mediate these effects are not known. However, potential candidates are maternal hyperleptinemia, hyperinsulinaemia, hyperglycaemia or maternal inflammation. These may represent targets for focussed intervention strategies during critical periods of development to ameliorate the rising prevalence of obesity in society. Maternal obesity and/over-nutrition predisposes offspring to obesity and type 2 diabetes Evidence from human studies Human epidemiological studies provide strong evidence for the heritability of obesity. For example, an American cohort of 854 participants showed that individuals had double the Maternal over-nutrition and offspring obesity predisposition K Rooney and SE Ozanne 884 risk of adult obesity if parental obesity was present.4 The environment shared within families during the post-natal developmental period is undoubtedly an important factor in the development of offspring obesity.7 However, the relationship between maternal obesity and offspring obesity is stronger than that of paternal obesity with the risk of extreme obesity (BMI 440) five times greater in relatives of extremely obese women.5 This could result from imprinting of maternal genes that influence energy balance, but a more widely accepted possibility is that the predisposition is mediated by the in utero environment a developing fetus in an obese woman is exposed to.6,8,9 Maternal obesity has been associated with offspring obesity at birth,10,11 childhood (2–9 years)12,13 and adolescence (14 years),14 suggesting that the effects are long lasting. Furthermore, children of obese mothers that were born large for gestational age are at twice the risk of developing insulin resistance accompanying childhood obesity (11 years).15 The underlying mechanisms by which maternal obesity confers this risk of obesity to offspring is unknown. There are a number of components of maternal obesity that have been associated with offspring obesity and metabolic health. These include pre-pregnancy BMI,16,17 maternal weight gain,18 as well as consumption of an obesogenic diet. Dis-entangling how these related parameters mediate their effects on offspring health is therefore extremely complex and will only be defined by intervention studies targeted at individual components. All of these factors are associated with similar metabolic perturbations including hyperglycaemia, hyperinsulinaemia and hyperleptinaemia (reviewed in Weissgerber et al.19). Therefore, it is perhaps not too surprising that associations between maternal hyperglycaemia,20,21 insulin resistance15 and hyperleptinaemia and offspring adiposity have all been reported. The growing prevalence of obesity and its accompanying complications in women of childbearing age is therefore of a major concern. Increasing attention towards interventions that may be used to improve maternal health could, therefore, impact substantially on offspring health both in the short and long term. A number of early reviews,19,22–25 in addition to two recent studies,26,27 have identified altering maternal carbohydrate intake as well as maternal physical activity levels as potential strategies for positively regulating maternal weight gain and o (...truncated)