Transgenerational effects of obesogens

Abstract

Obesity and associated disorders are now a global pandemic. The prevailing clinical model for obesity is overconsumption of calorie‐dense food and diminished physical activity (the calories in—calories out model). However, this explanation does not account for numerous recent research findings demonstrating that a variety of environmental factors can be superimposed on diet and exercise to influence the development of obesity. The environmental obesogen model proposes that exposure to chemical obesogens during in utero and/or early life can strongly influence later predisposition to obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage, in vivo either directly or indirectly. Numerous obesogens have been identified in recent years and some of these elicit transgenerational effects on obesity as well as a variety of health end‐points after exposure of pregnant F0 females. Prenatal exposure to environmental obesogens can produce lasting effects on the exposed animals and their offspring to at least the F4 generation. Recent results show that some of these transgenerational effects of obesogen exposure can be carried across the generations via alterations in chromatin structure and accessibility. That some chemicals can have permanent effects on the offspring of exposed animals suggests increased caution in the debate about whether and to what extent exposure to endocrine‐disrupting chemicals and obesogens should be regulated.

Tributyltin chloride (TBT) induces RXRA down-regulation and lipid accumulation in human liver cells

“…e ., obesity and diabetes etc.) has been under extensive investigation for many years [3,6,37]. In particular, a growing class of endocrine disrupting chemicals, termed obesogens [12], has been singled out as a subset of chemicals with potential of increasing adiposity via altering lipid homeostasis and adipogenesis [3,38,39], but also exhibiting additional, systemic effects in other tissues ( i .…”

“…e ., pancreas, liver, muscle, etc.). The effects of obesogens are also dependent upon when exposure occurs, with early-life developmental stages being more susceptible [6,16,40]. Tributyltin, an organotin that has been used as a biocide for many decades, is considered a prototypical tool obesogenic compound.…”

“…Endocrine disrupting chemicals (EDCs) are a growing class of compounds with highly varied structures and mechanisms of action that interfere with endocrine and metabolic functions by posing as either agonists or antagonists of physiological hormones [1,2]. A subset of these compounds has been termed “obesogens” as they contribute to metabolic imbalance and obesity, especially when exposure occurs at sensitive developmental windows [3–6]. Obesogenic compounds are comprised of many different classes of environmental pollutants and industrial products, including cigarette smoke, estrogenic compounds, flame retardants and plasticizers; however, improved assays to accurately determine if compounds are indeed potential obesogens continue to be in demand [7].…”

Human Health Consequences of Endocrine-Disrupting Chemicals

“…Obesogens have several target tissues including adipose tissue, brain, liver, stomach, and pancreas. At the level of adipose tissue, obesogens promote obesity by inducing an increase in the number of adipocytes (by activating nuclear receptor signaling pathways critical for adipogenesis) and storage of fat (Figure 4) [17].…”

Development priority

“…The summary report emphasized the timescales, as developmental toxicity can result in lasting deficits and elevated risks of disease that may appear much later. Particularly worrisome are endocrine disruption effects, some of which may lead to transgenerational effects driven through epigenetic reprogramming of germ cells and stem cells. Air pollution is a global concern as an involuntary exposure, and exposures during early development appear to be particularly hazardous, though not yet recognized by regulatory agencies .…”