Developmental programming by maternal obesity: Lessons from animal models

Abstract

The obesity epidemic has led to more women entering pregnancy overweight or obese. In addition to adverse short-term outcomes, maternal obesity and/or gestational diabetes predispose offspring to developing obesity, type 2 diabetes and cardiovascular disease in adulthood through developmental programming. Human epidemiological studies, although vital in identifying associations, are often unable to address causality and mechanistic studies can be limited by the lack of accessibility of key metabolic tissues. Furthermore, multi-generational studies take many years to complete. Integration of findings from human studies with those from animal models has therefore been critical in moving forward this field that has been termed the 'Developmental Origins of Health and Disease'. This review summarises the evidence from animal models and highlights how animal models provide valuable insight into the maternal factors responsible for developmental programming, potential critical developmental windows, sexual dimorphism, molecular mechanisms and age-related offspring outcomes throughout life. Moreover, we describe how animal models are vital to explore clinically relevant interventions to prevent adverse offspring outcomes in obese or glucose intolerant pregnancy, such as antioxidant supplementation, exercise and maternal metformin treatment.

Keywords: animal models; exercise; interventions; metabolic syndrome; metformin; obesity; preclinical.