Endocrine disrupting chemicals: Friend or foe to brown and beige adipose tissue?

Abstract

The effects of Endocrine Disrupting Chemicals (EDCs) on the current obesity epidemic is a growing field of interest. Numerous EDCs have shown the potential to alter energy metabolism, which may increase the risk of obesity, in part, through direct actions on adipose tissue. While white adipose tissue has historically been the primary focus of this work, evidence of the EDC-induced disruption of brown and beige adipose tissues continues to build. Both brown and beige fat are thermogenic adipose depots rich in mitochondria that dispense heat when activated. Due to these properties, brown and beige fat are implicated in metabolic diseases such as obesity, diabetes, and cachexia. This review delves into the current literature of different EDCs, including bisphenols, dioxins, air pollutants, phthalates, and phytochemicals. The possible implications that these EDCs have on thermogenic adipose tissues are covered. This review also introduces the possibility of using brown and beige fat as a therapeutic target organ by taking advantage of some of the properties of EDCs. Collectively, we provide a comprehensive discussion of the evidence of EDC disruption in white, brown, and beige fat and highlight gaps worthy of further exploration.

Keywords: Beige adipose tissue; Brown adipose tissue; Endocrine disrupting chemicals; Obesity; Phytochemicals.

Figure 1:

Major signaling pathways involved in the regulation of brown and beige adipose tissue activity. Abbreviations: β-Adrenergic Receptor (β-AR), CCAAT-enhancer-binding proteins (C/EBP), cyclic adenosine monophosphate (cAMP), cAMP-response element binding protein (CREB), Type II iodothyronine deiodinase (DIO2), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), peroxisome proliferator-activated receptor (PPAR), triiodothyronine (T3), thyroxine (T4), G-protein-coupled bile acid receptor (TGR5), thyroid receptor (TR).

Figure 2:

Summary of potential points where synthetic and natural EDCs may alter brown and beige adipogenesis.

Figure 3:

Word cloud of keywords derived from manuscripts that investigated the effects of bisphenols, dioxins, air pollutants, or phthalates on brown or beige adipose tissues. Studies were collated from Web of Science, split by year, and keywords were pulled to generate word clouds.

Figure 4:

Number of publications by year that study the effects of bisphenols, dioxins, air pollutants, or phthalates on brown or beige adipose tissues. Databases searched included PubMed, Web of Science, and ProQuest. Following de-duplication, a total of 126 citations were found. Of note, phytochemicals were not included in this list due to the vast array of chemicals within this class and large number of publications in this area.