Maternal Environment and the Transgenerational Cycle of Obesity and Diabetes

摘要

The prevalence of obesity continues to increase worldwide and represents one of the most pressing public health issues due to its associated morbidity, mortality, and health care costs. Novel research is demonstrating that alterations of the maternal environment can impact the intrauterine development of the fetus and influence the offspring's risk for obesity and type 2 diabetes over the lifecourse. This article reviews the epidemiological evidence with a focus on the fetal overnutrition hypothesis. We discuss potential mechanisms and suggest future directions for research. THE FETAL OVERNUTRITION PATHWAY TO OBESITY While postnatal lifestyle is the most immediate cause of obesity, the influence of the maternal in utero environment is evidenced in the U- or J-shaped relationship between birth weight and adult obesity and metabolic disease demonstrating that both a nutritionally limited or excessive in utero environment can lead to postnatal obesity and related chronic diseases. Developmental biology has taught us about the role of a mismatch between a constrained prenatal and a plentiful postnatal environment in the patho-genesis of obesity, i.e., a so-called thrifty obesity pathway (1). This is likely operating in developing countries and populations undergoing rapid transition. Another developmental pathway to obesity, which is likely more important in Western societies, is the fetal overnutrition pathway. This pathway reflects the effects of hypernutrition during fetal life and creates the conditions for the later patho-physiological effects of an obesogenic environment (1). Although these developmental mechanisms are likely distinct, they are both associated with an increased risk of obesity later in life. This article focuses on the fetal over-nutrition pathway.