Developmental and Transmittable Origins of Obesity-Associated Health Disorders

Abstract

The current global obesity pandemic is clearly linked to both the increasing prevalence of, and preference for, foods high in calories, specifically fat and sucrose, and declining levels of daily physical activity. A less commonly discussed possible explanation is that risk of obesity begins in utero as a result of developmental plasticity during early life. This idea fits into the broader Developmental Origins of Health and Diseases (DOHAD) hypothesis, which holds that stressful in utero exposure manifests as disease in adulthood. In this review, we highlight several studies that have revealed the role of epigenetics in multigenerational transmission of developmentally programmed obesity and associated cardiometabolic disease.

Fig. 1

A schematic of possible maternal overnutrition influences on mitochondrial dysfunction in all tissues of the offspring. In a maternal obesogenic environment, offspring cells could inherit in a germline fashion malfunctioning mitochondria and/or deregulated epigenetic signatures. These alterations contribute to a phenotype of impaired mitochonodrial function for several generations. To be considered transgenerational transmission due to maternal obesity and overnutrition in this example, the inherited traits must be apparent in the F3 generation since the F1 embryo and F2 primordial germ cells are directly exposed to a given environmental factor in utero. In such cases, a change must occur in the germline to allow the effect to persist through three generations.