Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today

Department of Developmental and Cell Biology, University of California, Irvine, 92697-2300, USA.
Birth Defects Research Part C Embryo Today Reviews (Impact Factor: 2.63). 03/2011; 93(1):34-50. DOI: 10.1002/bdrc.20197
Source: PubMed


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.

Download full-text


Available from: Amanda Janesick
  • Source
    • "Obesity is a growing public health problem worldwide (Booth et al. 2001; Lobstein 2004; Popkin and Doak 1998). Although obesity is primarily attributable to genetic predisposition, high calorie intake, and insufficient physical activity, exposure to endocrine-disrupting chemicals such as PBDEs may also play a role (Janesick and Blumberg 2011a; Legler and Brouwer 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems. In this study, we examined whether pre- and post-natal exposure to the components of penta-BDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California. We measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index at age 7. Maternal PBDE serum levels during pregnancy were associated with higher body mass index (BMI) z-scores in boys (BMI z-score βadjusted = 0.26; 95% CI: -0.19, 0.72) but lower scores in girls (BMI z-score βadjusted = -0.41; 95% CI: -0.87, -0.05) at 7 years of age (pinteraction= 0.04). In addition, child's serum BDE-153 concentration (log10), but not other penta-BDE congeners, demonstrated inverse associations with body mass index at age 7 (BMI z-score βadjusted= -1.15, 95% CI -1.53, -0.77) but there was no interaction by sex. We estimated sex-specific associations with maternal PBDE levels during pregnancy and body mass index at age 7 with positive associations in boys and negative associations in girls. Children's serum BDE-153 concentrations were inversely associated with body mass index at age 7 with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.
    Full-text · Article · Feb 2015 · Environmental Health Perspectives
  • Source
    • "Nevertheless, some studies have demonstrated the effect of fat or simple carbohydrate overconsumption on body composition and on global adipose tissue gene expression [4], the effect of a high-sugar diet (HSD) after weaning on adipogenesis and its impact on adult life remains unclear. Adipogenesis is a tightly regulated molecular process controlling the conversion of precursor cells to mature adipocytes [16] [17]. The transcriptional cascade regulating adipose differentiation is controlled in a sequential manner, where factors enhance or repress the expression of each other [18]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Scope: We have previously shown an increase in adipocyte size and lipid content in retroperitoneal white adipose tissue (rWAT) induced by an 8-week high-sugar diet (HSD). In this study, we assessed the effect of a HSD on the transcriptional activity of adipogenic genes in a time-course study to provide insight regarding the genetic networks involved in the rWAT response to dietary sugar. Methods and results: Weaned male Wistar rats were fed a standard chow diet or HSD (68% carbohydrates) for 4, 8 or 12 weeks, and rWAT was removed for histopathology and PCR array (adipogenesis) analyses. The HSD induced adipocyte hypertrophy and hyperplasia in rWAT after 12 weeks of ingestion. Additionally, the HSD altered serum VLDL-cholesterol, triacylglycerol and glucometabolic parameters. Hierarchical clustering revealed HSD-induced changes in the expression patterns of the tested gene set. Pathway analysis, which used the enrichment analysis algorithm of the Thompson Reuters MetaCore platform, associated a cluster of differentially expressed genes with canonical pathways related to regulating adipocyte differentiation and proliferation (p-value < 10(-7)). Conclusion: HSD feeding post-weaning increased both the adipocyte size and number by simultaneously up-regulating pro-adipogenic signals (the PPARγ pathway) and down-regulating anti-adipogenic signals (Wnt pathway) in young adults.
    Full-text · Article · Dec 2014 · Molecular Nutrition & Food Research
  • Source
    • "In recent years, it has become increasingly clear that various aspects of the intrauterine environment, such as exposure to environmental pollutants, influence the developmental origins of obesity and other risk factors for cardiovascular disease (Janesick and Blumberg, 2011a,b; La Merrill and Birnbaum, 2011). Maternal smoking during pregnancy is associated with increased risk of obesity, diabetes, and hypertension in offspring (Ino, 2010; Morley et al., 1995; Oken et al., 2005; Power and Jefferis, 2002). "

    Full-text · Conference Paper · Sep 2014
Show more