The “Toxic” Effects of a Perinatal Obesogenic Environment: Maternal Obesity and Impacts on Future Generations

In recent decades, epidemic levels of metabolic disease states have become global issues. Among the most well-known of these are obesity, diabetes, and cardiovascular diseases, whose social and economic impacts have prompted a global fervor of investigation into their causes. Though initially considered to be determined largely by genetic and lifestyle factors, such as diet and exercise, this paradigm would ultimately be insufficient to explain the continued propagation of non-communicable diseases. In the late 1980s, a new and exciting field of research described the roots of disease to be founded early in developmental life. These early studies showed that perturbations to the organism during critical developmental windows had long-term impacts on disease risk even after controlling for lifestyle and genetics. By extension, alterations in maternal physiology are implicated by this discovery, as it is the primary determinant of the fetal environment. Indeed, extensive data derived from animal models and clinical studies have been essential to defining the nature and extent of the influence that the mother’s own metabolic status has on the developing fetus. An altered substrate profile in cases of maternal obesity is said to “program” the offspring, resulting in a maladapted physiology and increased disease risk. A compelling case is then made for a metabolically abnormal intrauterine environment acting as a “toxin” for the fetus, initiating and driving later-in-life disease. The focus of this chapter will be to review the known complications of maternal high fat diet and obesity on offspring health in later life, and to describe recent mechanistic insights into its origins.