Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long‐term dietary administration

Abstract

The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole‐body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long‐term dietary consumption of DEP in adipocytes. DEP‐treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator‐activated receptor γ and its downstream insulin‐sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c‐Apaf1‐caspase 9‐caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.

The Role of Endocrine Disruptors Bisphenols and Phthalates in Obesity: Current Evidence, Perspectives and Controversies

“…BPA and phthalates may induce the expression and secretion of certain proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α and downregulate the expression of anti-inflammatory adipokines such as adiponectin, leading to a sustained low-grade inflammation both locally and systematically, adipose dysfunction and insulin resistance [ 84 , 116 , 117 ]. Nevertheless, the mechanisms implicated in metabolic inflammation are still under investigation.…”