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

Abstract

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 (ERα and ERβ) 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 β-oxidation and synthesis, by estrogens and then examined the disturbance of E2/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.

Prostate Stem Cell Antigen Single Nucleotide Polymorphisms Influence Risk of Estrogen Receptor Negative Breast Cancer in Korean Females

“…Meanwhile the association of genetic polymorphisms (eg. CYP19A1) with aromatase activity is correlated with sex hormones levels and estrogendependent cancer such as breast cancer and prostatic cancer (Chen et al, 2009;Czajka-Oraniec and Simpson, 2010). While antihormone drug (SERMs, SERD and AIs) do prevent the development of many ER (+) breast cancers, these drugs do not prevent ER (-) breast cancer.…”

Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function

“…Moreover, E 2 has recently been linked to alterations in whole body glucose homeostasis [41]. The most powerful evidence comes from situations where oestrogen levels are outside the physiological range, such as in menopause or pregnancy.…”

Estradiol stimulates mitochondrial biogenesis and adiponectin expression in skeletal muscle

“…E 2 also plays a role in the regulation of body weight, and a loss of E 2 is associated with the development of obesity (Chen et al 2009), which is related to a decrease in adiponectin levels in serum. Adiponectin is an insulinsensitizing hormone secreted mainly by white adipose tissue (WAT; Harwood 2012).…”