Perinatal exposure to DES and latent development of high body weight and obesity
Abstract from “Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement”, 2009
White adipose tissue metabolism is under the control of the sympathetic nervous system and is modulated by hormones including sex steroids. The impact of environmental estrogens on adipose tissue may be through direct modulation of lipogenesis, lipolysis, and adipogenesis, or indirect by affecting food consumption and leptin secretion targeting the central nervous system or lipid homeostasis in liver.
The estrogenic pharmaceutical chemical DES illuminates the relationship between perinatal exposures and latent development of high body weight and obesity. Moreover, there is a complex relationship between the concentration of estrogen to which pregnant animals are exposed and the weight of the offspring in adulthood. Specifically, according to a recent experiment by Newbold et al., mice neonatally exposed to DES experience increased body weight in adulthood associated with excess abdominal body fat. Interestingly, the dose of DES determines the chronic manifestation of the observed alterations, with high doses leading to initially decreased body weight and a peripubertal “catch-up” and low doses causing an increase in weight detectable only in adulthood. Moreover, the timing is important because gestational administration in rodents results in the offspring’s low birth weight, an unchanged metabolic characteristic throughout life. Along with an increase in body fat stores, the adipokines leptin and adiponectin, IL-6 (an inflammatory marker), and triglycerides were all elevated in DES-exposed mice.
An in vitro study using a culture system of 3T3-L1 preadipocytes showed that 4-nonylphenol and BPA stimulated lipid accumulation, accelerating their differentiation to mature adipocytes in a time- and concentration-dependent way. The underlying mechanism appeared to involve up-regulation of gene expression involved in lipid metabolism and adipocyte differentiation. In the second part of the experiment, fat accumulation was observed in human hepatocellular carcinoma cell lines exposed to those endocrine disruptors. These findings are consistent with previous in vitro studies using mouse fibroblast cell lines in which a link between environmental chemicals including nonylphenol, BPA, and genistein in the development of body weight imbalance was suggested.
- Full study (free access) : Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement, Endocrine Society endocrine reviews, PMC2726844, 2009 Jun.