Long-term bisphenol A exposure exacerbates diet-induced prediabetes via TLR4-dependent hypothalamic inflammation.

Abstract

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has been revealed associated with metabolic disorders such as obesity, prediabetes, and type 2 diabetes (T2D). However, its underlying mechanisms are still not fully understood. Here, we provide new evidence that BPA is a risk factor for T2D from a case-control study. To explore the detailed mechanisms, we used two types of diet models, standard diet (SD) and high-fat diet (HFD), to study the effects of long-term BPA exposure on prediabetes in 4-week-old mice. We found that BPA exposure for 12 weeks exacerbated HFD-induced prediabetic symptoms. Female mice showed increased body mass, serum insulin level, and impaired glucose tolerance, while male mice only exhibited impaired glucose tolerance. No change was found in SD-fed mice. Besides, BPA exposure enhanced astrocyte-dependent hypothalamic inflammation in both male and female mice, which impaired proopiomelanocortin (POMC) neuron functions. Moreover, eliminating inflammation by toll-like receptor 4 (TLR4) knockout significantly abolished the effects of BPA on the hypothalamus and diet-induced prediabetes. Taken together, our data establish a key role for TLR4-dependent hypothalamic inflammation in regulating the effects of BPA on prediabetes.

• Authors: Qinlong Ma, Ping Deng, Min Lin, Lingling Yang, Le Li, Lu Guo, Lei Zhang, Mindi He, Yonghui Lu, Huifeng Pi, Yanwen Zhang, Zhengping Yu, Chunhai Chen, Zhou Zhou
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 402 Pg. 123926 (01 15 2021) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 33254826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Phenols
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• bisphenol A

Topics

• Animals
• Benzhydryl Compounds (toxicity)
• Case-Control Studies
• Diabetes Mellitus, Type 2
• Female
• Hypothalamus (metabolism)
• Inflammation (chemically induced)
• Male
• Mice
• Mice, Inbred C57BL
• Phenols
• Prediabetic State (chemically induced)
• Toll-Like Receptor 4 (genetics, metabolism)