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Environmental toxins contribute to obesity and metabolic diseases
In a recent study published in the Current Opinion in Pharmacology journal, researchers examined the effects of environmental toxins and brown adipose tissue (BAT) on obesity and metabolic disorders. Obesity results from higher energy intake compared to energy expenditure, which in turn leads to an increase in obesity. The calorie gap to prevent weight gain is only 8.2 to 61.2 kcal/day in various populations. A sedentary lifestyle and excessive energy expenditure may not be entirely responsible for the increasing prevalence of global obesity and associated metabolic diseases, despite the robustness with which energy balance is regulated. It is interesting to note that in addition to people, many...
Environmental toxins contribute to obesity and metabolic diseases
In a recently published study in the Current opinion in pharmacology Journal, researchers examined the effects of environmental toxins and brown adipose tissue (BAT) on obesity and metabolic disorders.
Obesity results from higher energy intake compared to energy expenditure, which in turn leads to an increase in obesity. The calorie gap to prevent weight gain is only 8.2 to 61.2 kcal/day in various populations. A sedentary lifestyle and excessive energy expenditure may not be entirely responsible for the increasing prevalence of global obesity and associated metabolic diseases, despite the robustness with which energy balance is regulated. It is interesting to note that many other species besides humans appear to develop obesity. These results suggest that factors other than increased availability of high-calorie foods and reduced mobility caused by technological advances may also contribute to obesity.
BAT and thermogenesis and obesity prevention
The primary site for the accumulation of lipophilic environmental compounds is adipose tissue. BAT and white adipose tissue (WAT) are two different forms of adipose tissue. Only eutherian mammals have BAT, which, unlike WAT, has a thermogenic function that gives animals an evolutionary advantage in the cold.
Thermogenic activities performed by active BAT per gram of tissue oxidize plasma triglycerides and glucose at a relatively high rate. However, it should be noted that skeletal muscle-based thermogenesis contributes significantly more to energy expenditure during cold exposure due to its large mass. Four weeks of cold acclimation is enough for adults to increase BAT thermogenesis and reduce skeletal muscle shivering. This highlights the potential importance of BAT for whole-body energy expenditure. In contrast, inhibition of adipose tissue lipolysis reduces BAT thermogenesis and promotes muscle tremors.
Studies suggest that uncoupling of protein 1 (UCP1) and BAT also promotes energy expenditure in humans, independent of cold exposure, by increasing diet-induced thermogenesis (DIT). DIT accounts for 5% to 15% of daily energy expenditure, depending on the composition and amount of food consumed. Additionally, a study showed that eating a meal rapidly increases blood flow and oxygen consumption in BAT. As a result, DIT thermogenesis could play a significant role in human daily energy expenditure when residing in thermoneutral environments. Therefore, inhibition of this process could be associated with obesity and metabolic disorders.
The pesticide chlorpyrifos inhibits diet-induced thermogenesis in BAT
The team examined brown adipocytes expressing the luciferase-associated UCP1 promoter to identify environmental contaminants that could directly affect BAT function. A total of 34 widely used pesticides were studied, including food packaging materials, herbicides and food dyes, that had structural similarities to serotonin, a substance that inhibits BAT thermogenesis. The team found that UCP1 promoter activity and protein and messenger ribonucleic acid (mRNA) expression were dramatically reduced in the presence of chlorpyrifos (CPF) at doses as low as 1 pM. CPF, an organophosphate insecticide, is often applied to various crops and fruits to control pests.
After treatment with 1 pM CPF, BAT cells were subjected to unbiased RNA sequencing, which revealed that the low dose of CPF caused noticeable changes in mitochondrial gene expression. Subsequent research revealed that these changes were associated with deficits in mitochondrial respiration. These results showed that CPF suppressed UCP1 expression and thermogenesis in cultured BAT cells within the exposure window in which individuals can be exposed to CPF through ingestion of fruits and vegetables.
The team found that high doses of CPF, which block brain and plasma acetylcholinesterase activity and plasma butyrylcholinesterase, can cause obesity and glucose dysregulation through mechanisms that may include changes in gut flora or an increase in calorie expenditure. However, weight gain, glucose intolerance, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) have also been reported at low doses of CPF when test mice were maintained at thermoneutrality. This suggested that CPF levels consistent with non-occupational exposure in individuals could promote obesity by preventing diet-induced thermogenesis in BAT.
Other environmental pollutants that may affect BAT function
Many environmental toxins bind to hormone receptors such as androgen receptors (ARs), aryl hydrocarbon receptors (AhR), estrogen receptors (ERs), estrogen receptor-related receptors (ERRs), thyroid receptors (TRs), and pregnane X receptors (PXR). ) interferes with hormonal effects. These receptors play a crucial role in the control of BAT thermogenesis. Environmental toxins include DDT, organochlorine, and vinclozolin, which block androgen receptor-mediated processes, including UCP1 transcription.
Some environmental toxins can affect BAT thermogenesis by mimicking the effects of estrogen. For example, the most popular industrial chemical used in the production of plastics, bisphenol A (BPA), causes weight loss without altering calorie intake. Furthermore, maternal exposure to BPA at the time of pregnancy mimics a weak estrogen agonist, increasing BAT interscapular weight and upregulating UCP1 expression in female offspring, but decreasing BAT activity and brown adipogenesis in male offspring.
Overall, the study results showed that certain environmental pollutants could inhibit BAT thermogenesis. Further studies should be performed at different doses in BAT cell lines to evaluate this possibility and ensure more precise translatability to humans.
Reference:
- Bo Wang, Gregory R. Steinberg, Umweltgifte, braunes Fettgewebe und mögliche Verbindungen zu Fettleibigkeit und Stoffwechselerkrankungen, Current Opinion in Pharmacology, Band 67, 2022, 102314, ISSN 1471-4892, DOI: https://doi.org/10.1016/j.coph.2022.102314, https://www.sciencedirect.com/science/article/pii/S1471489222001412
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