Adipocytes under assault: Environmental disruption of adipose physiology

Abstract

The burgeoning obesity epidemic has placed enormous strains on individual and societal health mandating a careful search for pathogenic factors, including the contributions made by endocrine disrupting chemicals (EDCs). In addition to evidence that some exogenous chemicals have the capacity to modulate classical hormonal signaling axes, there is mounting evidence that several EDCs can also disrupt metabolic pathways and alter energy homeostasis. Adipose tissue appears to be a particularly important target of these metabolic disruptions. A diverse array of compounds has been shown to alter adipocyte differentiation, and several EDCs have been shown to modulate adipocyte physiology, including adipocytic insulin action and adipokine secretion. This rapidly emerging evidence demonstrating that environmental contaminants alter adipocyte function emphasizes the potential role that disruption of adipose physiology by EDCs may play in the global epidemic of metabolic disease. Further work is required to better characterize the molecular targets responsible for mediating the effects of EDCs on adipose tissue. Improved understanding of the precise signaling pathways altered by exposure to environmental contaminants will enhance our understanding of which chemicals pose a threat to metabolic health and how those compounds synergize with lifestyle factors to promote obesity and its associated complications. This knowledge may also improve our capacity to predict which synthetic compounds may alter energy homeostasis before they are released into the environment while also providing critical evidentiary support for efforts to restrict the production and use of chemicals that pose the greatest threat to human metabolic health.

Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE

“…Supporting these warnings are, among others, several epidemiological and in vivo studies that reported the positive correlation of EDCs concentrations, both in AT and plasma, with the prevalence of obesity, MetS, insulin resistance, hypertension and CVD 21–23 , as well as adipocyte dysfunction 24 .…”

Biomarkers Linking PCB Exposure and Obesity.

“…Several mechanisms are plausible. EDCs have been shown to alter the differentiation of adipocytes [65, 66]. EDCs are capable of mediating changes in methylation patterns and regulate epigenetic encoding in cells, and epigenetic program control by such compounds are now well documented [67–70].…”

PCB126 inhibits adipogenesis of human preadipocytes

“…Adipocytes producing normal levels of both leptin and adiponectin are thus essential for effective insulin signaling, and their dysfunction leads to disruption of insulin signaling (Mlinar and Marc, 2011). Adipocytes and fat tissue in general accumulate lipophilic toxicants such as PCBs and thus are likely to be affected by them (Regnier and Sargis, 2014). …”