Transgenerational inheritance of prenatal obesogen exposure

Abstract

Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. The generally accepted cause of obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in - calories out model). However, emerging evidence demonstrates that environmental factors can predispose exposed individuals to gain weight, irrespective of diet and exercise. The environmental obesogen model proposes that chemical exposure during critical stages in development can influence subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage. Numerous obesogens have been identified in recent years and some of these have been shown to act through the peroxisome proliferator activated receptor, the master regulator of adipogenesis. Others act through as yet unidentified pathways. Notably, some of these obesogens elicit transgenerational effects on a variety of health endpoints, including obesity in offspring after exposure of pregnant F0 females. Thus, prenatal exposure to xenobiotic compounds can have lasting, potentially permanent effects on the offspring of exposed animals. Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated.

The Epidemiology of Obesity: A Big Picture

“…In addition, parental diet, lifestyle, and other exposures have been implicated in subsequent offspring obesity risk, including famine exposure (30), parental obesity (31–33), smoking (34), endocrine-disrupting and other chemicals (35,36), and weight gain during gestation and gestational diabetes (33,37). These and other studies point to lasting effects of fetal programming that via differing mechanisms, likely epigenetic, result in substantial repercussions in life course health, with implications across the socioeconomic/food availability spectrum.…”

“…Further, we do not address the body of growing evidence on the role of environmental pollutants–“obesogens”–in obesity, specifically those known as endocrine-disrupting chemicals. We refer readers to recent reviews on the topic (35,36,65). …”

Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation

“…In addition to food and physical activity, a variety of other environmental factors such as less sleep time, endocrine disruptors (also called obesogens) , epigenetic and intergenerational effects, older parental age, certain medications and reduced smoking have all conspired to enhance the effects from the main causative agents – tasty and pleasurable food and low physical activity .…”

Transgenerational effects of obesogens and the obesity epidemic

“…Despite increased public awareness of the problem, the obesity epidemic continues unabated and the medical community is finally beginning to consider the possibility that there may be more to obesity than “calories in-calories out”. Work in our laboratory and in other labs around the world has identified obesogenic chemicals that can predispose exposed animals to accumulate more fat and these effects can be transmitted to their descendents [reviewed in 40,75]. The precise etiology of weight gain in exposed animals is uncertain – it could be that some eat more and exercise less – but this misses the point.…”