Bhavana Kunkalikar via News-Medical – In a recent study published in the Current Opinion in Pharmacology journal, researchers assessed the impact of environmental toxicants and brown adipose tissue (BAT) on obesity and metabolic disorders.
Obesity results from higher energy intake compared to energy expenditure, which in turn results in an increase in adiposity. The calorie gap for preventing weight gain in various populations is only 8.2 to 61.2 kcal/day. A sedentary lifestyle and excessive energy consumption may not entirely account for the increasing prevalence of global obesity and accompanying metabolic diseases, despite the robustness with which energy balance is regulated. It’s interesting to note that many other species also seem to be developing obesity in addition to humans. These findings imply that other factors may also contribute to obesity, other than the increased availability of high-calorie foods and the decreased mobility caused by technology advancements.
BAT and Thermogenesis and Prevention of Obesity
The primary location for the accumulation of lipophilic environmental compounds is adipose tissue. BAT and white adipose tissue (WAT) are two different adipose tissue forms. 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 during exposure to cold, skeletal muscle-based thermogenesis contributes significantly more to energy expenditure because of its large bulk. Four weeks of acclimation to cold is sufficient for adults to increase BAT thermogenesis and decrease skeletal muscle shivering. This highlights the potential significance of BAT concerning whole-body energy expenditure. In contrast, inhibition of adipose tissue lipolysis decreases BAT thermogenesis and promotes muscle shivering.
Studies suggest that uncoupling protein 1 (UCP1) and BAT also promote energy expenditure in humans, regardless of cold exposure by boosting diet-induced thermogenesis (DIT). DIT accounts for 5% to 15% of the daily energy expenditure, depending on the make-up and quantity of the food consumed. In addition, a study showed that consuming a meal rapidly increases blood flow and oxygen consumption in BAT. As a result, DIT thermogenesis might play a significant role in humans’ daily expenditure of energy when they are in thermoneutral environments. Therefore, inhibition of this process might be linked to obesity and metabolic disorders.
The Pesticide Chlorpyrifos Inhibits Diet-Induced Thermogenesis in BAT
The team screened brown adipocytes expressing the UCP1 promoter associated with luciferase to identify environmental contaminants that could directly decrease BAT function. A total of 34 widely used pesticides were screened, including food packaging substances, herbicides, and food colors that shared structural similarities with serotonin, a substance that inhibited BAT thermogenesis. The team noted that UCP1 promoter activity, and protein and messenger ribonucleic acid (mRNA) expression, dramatically reduced in the presence of chlorpyrifos (CPF) at dosages as low as 1 pM. CPF, an organophosphate insecticide, is frequently applied to various field crops and fruits to control pests.
Following treatment with 1 pM CPF, BAT cells were subjected to unbiased RNA sequencing, which revealed that the low dose of CPF caused noticeable alterations in mitochondrial gene expression. Subsequent research revealed that these changes were linked to deficits in mitochondrial respiration. These results demonstrated that CPF suppressed UCP1 expression and thermogenesis in cultured BAT cells within the exposure window within which individuals may be exposed to CPF through the ingestion of fruits and vegetables.
The team noted that high CPF doses, which block brain and plasma acetylcholinesterase activity and plasma butyrylcholinesterase, can induce obesity and glucose dysregulation via mechanisms that may involve changes to the gut flora or increase in caloric consumption. However, weight gain, glucose intolerance, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) were also reported at the low CPF doses when test mice were maintained at thermoneutrality. This indicated that CPF levels consistent with non-occupational exposure in individuals might encourage obesity by preventing diet-induced thermogenesis in BAT.
Other Environmental Pollutants Which May Inhibit BAT Function
Numerous 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) interfered with hormonal effects. These receptors play a crucial role in controlling BAT thermogenesis. Environmental toxins include DDT, organochlorine, and vinclozolin block androgen receptor-mediated processes, including UCP1 transcription.
Some environmental toxins may influence BAT thermogenesis by imitating estrogen’s actions. For instance, the most popular industrial chemical used in manufacturing plastics, bisphenol A (BPA), causes weight loss without altering caloric intake. In addition, maternal exposure to BPA at the time of pregnancy mimics a weak estrogen agonist, increasing interscapular BAT weight and upregulating UCP1 expression in female offspring but decreasing BAT activity and brown adipogenesis in male offspring.
Overall, the study findings highlighted that specific environmental contaminants might inhibit BAT’s thermogenesis. Further research should be conducted at different doses in BAT cell lines in order to assess this possibility and provide translatability to humans more accurately.
- Bo Wang, Gregory R. Steinberg, Environmental toxicants, brown adipose tissue, and potential links to obesity and metabolic disease, Current Opinion in Pharmacology, Volume 67, 2022, 102314, ISSN 1471-4892, DOI: https://doi.org/10.1016/j.coph.2022.102314, https://www.sciencedirect.com/science/article/pii/S1471489222001412
To read the original article click here.