增塑剂
内分泌学
细胞凋亡
邻苯二甲酸二乙酯
内科学
脂肪细胞
邻苯二甲酸盐
脂肪组织
炎症
期限(时间)
化学
医学
生物化学
物理
有机化学
量子力学
作者
Shirsha Mondal,Baldur van Lew,Songita Ghosh,Suktara Guria,Sutapa Mukherjee
摘要
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.
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