Regulation of energy metabolism pathways by estrogens and estrogenic chemicals and potential implications in obesity associated with increased exposure to endocrine disruptors.

The prevalence of obesity among children, adolescents and adults has been dramatically increasing worldwide during the last several decades. The obesity epidemic has been recognized as one of the major global health problems, because its health hazard is linked to a number of common diseases including breast and prostate cancers. Obesity is caused by combination of genetic and environmental factors. While genetic contribution to obesity has been known to be significant, the genetic factors remain relatively unchanged. Recent studies have highlighted the involvement of environmental "obesogens", i.e. the xenobiotic chemicals that can disrupt the normal development and homeostatic control over adipogenesis and energy balance. Several lines of evidence suggest that increasing exposure to chemicals with endocrine-disrupting activities (endocrine-disrupting chemicals, EDCs) contributes to the increased obesity. The cellular and molecular mechanisms underlying obesogen-associated obesity are just now being appreciated. In this paper, we comprehensively reviewed current knowledge about the role of estrogen receptors alpha and beta (ERalpha and ERbeta) in regulation of energy metabolism pathways, including glucose transport, glycolysis, tricarboxylic acid (TCA) cycle, mitochondrial respiratory chain (MRC), adenosine nucleotide translocator (ANT) and fatty acid beta-oxidation and synthesis, by estrogens; and then examined the disturbance of E(2)/ER-mediated energy metabolism pathways by environmental obesogens; and finally, we discussed the potential implications of disturbance of energy metabolism pathways by obesogens in obesity and pointed out several key aspects of this area that need to be further explored. A better understanding of the cellular and molecular mechanisms underlying obesogen-associated obesity will lead to new approaches for slow down and/or prevention of the increased trend of obesity associated with exposure to obesogens.