Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity

Abstract

Obesity and related disorders are a burgeoning public health epidemic, particularly in the U.S. Currently 34% of the U.S. population is clinically obese (BMI > 30) and 68% are overweight (BMI > 25), more than double the worldwide average and 10-fold higher than Japan and South Korea. Obesity occurs when energy intake exceeds energy expenditure; however, individuals vary widely in their propensity to gain weight and accrue fat mass, even at identical levels of excess caloric input. Clinical, epidemiological, and biological studies show that obesity is largely programmed during early life, including the intrauterine period. The environmental obesogen hypothesis holds that prenatal or early life exposure to certain endocrine disrupting chemicals can predispose exposed individuals to increased fat mass and obesity. Obesogen exposure can alter the epigenome of multipotent stromal stem cells, biasing them toward the adipocyte lineage at the expense of bone. Hence, humans exposed to obesogens during early life might have an altered stem cell compartment, which is preprogrammed toward an adipogenic fate. This results in a higher steady state number of adipocytes and potentially a lifelong struggle to maintain a healthy weight, which can be exacerbated by societal influences that promote poor diet and inadequate exercise. This review focuses on the developmental origins of the adipocyte, the relationship between adipocyte number and obesity, and how obesogenic chemicals may interfere with the highly efficient homeostatic mechanisms regulating adipocyte number and energy balance.

Association Between Urinary Bisphenol A Concentration and Obesity Prevalence in Children and Adolescents

“…28,29 Endocrine-disrupting chemicals such as BPA may have their greatest effect in early life 30 rather than in the period from ages 6 through 19 years examined in this study.…”

Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation in 3T3-L1 adipocytes

“…9,10) Obesogens are defined functionally as chemicals that promote obesity by increasing the number of fat cells or the storage of fat into existing fat cells. 11) Tributyltin chloride and tetrabromobisphenol A (a halogenated analog of bisphenol A) are representative obesogens that act as agonistic ligands of peroxisome proliferatoractivated receptor γ (PPAR γ), which is a transcription factor that plays a central role in adipocyte differentiation, lipid biosynthesis, and lipid storage. 12,13) Although PFOA has been reported to exhibit obesogenic properties such as an increased risk for obesity and body weight (BW) gain, 9,10) these mechanisms remain unclear, as there have been relatively few studies on the effects of PFOA on adipocytes and PPAR γ.…”

Are Environmental Contaminants Responsible for ‘Globesity’?

“…Recent human epidemiological studies have linked the presence of xenobiotic chemicals with increased body mass in humans [43]. Some of them are listed in Table 1.…”