Environmental toxicants contribute to obesity and metabolic disease

In a recent study published in Current opinion in pharmacology Journal, researchers evaluated 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, resulting in increased obesity. The calorie gap to prevent weight gain in various populations is only 8.2-61.2 kcal per day. Despite a stably regulated energy balance, sedentary lifestyles and excessive energy expenditure cannot fully explain the increasing prevalence of obesity and associated metabolic diseases worldwide. There is a possibility. It is interesting to note that in addition to humans, many other species also seem to develop obesity. It suggests that other factors besides a decline in obesity may also contribute to obesity.

Research: Ecotoxicants, Brown Adipose Tissue, and Potential Links to Obesity and Metabolic Disorders. Image Credit: Suzanne Tucker / Shutterstock

Prevention of BAT and thermogenesis and obesity

Adipose tissue is the main location for the accumulation of lipophilic environmental compounds. BAT and white adipose tissue (WAT) are two different forms of adipose tissue. Only eutherian mammals have BAT. BAT, unlike WAT, has a thermogenic function that gives animals an evolutionary advantage in the cold.

The thermogenic activity carried out by active BAT per gram of tissue oxidizes plasma triglycerides and glucose at relatively high rates. However, it should be noted that during cold exposure, skeletal muscle-based thermogenesis makes a significant contribution to energy expenditure due to its large volume. Four weeks of acclimating him to the cold is sufficient to reduce skeletal muscle shivering. This highlights the potential importance of her BAT on whole-body energy expenditure. In contrast, inhibiting adipose tissue lipolysis reduces BAT thermogenesis and promotes muscle shivering.

Studies suggest that the separation of protein 1 (UCP1) and BAT also promotes energy expenditure in humans, regardless of cold exposure, by enhancing diet-induced thermogenesis (DIT). DIT accounts for 5% to 15% of daily energy expenditure, depending on composition and amount of food consumed. Furthermore, one study showed that BAT blood flow and oxygen consumption rapidly increased when food was ingested. may play an important role in the daily energy expenditure of Inhibition of this process may therefore be associated with obesity and metabolic disorders.

The insecticide chlorpyrifos inhibits diet-induced thermogenesis in BAT

The team screened brown adipocytes expressing the luciferase-associated UCP1 promoter to identify environmental contaminants that could directly reduce BAT function. A total of 34 widely used pesticides were screened, including food packaging substances, herbicides, and food colorings that share structural similarities with serotonin, a substance that inhibits BAT’s thermogenesis. , 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. CPFs are frequently applied to various crops and fruits to control pests.

After treatment with 1 pM CPF, BAT cells were subjected to unbiased RNA sequencing, revealing that low doses of CPF caused marked changes in mitochondrial gene expression. Subsequent studies revealed that these changes were associated with defects in mitochondrial respiration. These results indicate that CPF suppressed UCP1 expression and thermogenesis in cultured BAT cells within an exposure window in which individuals may be exposed to CPF through ingestion of fruits and vegetables.

The team found that high-dose CPF, which blocks brain and plasma acetylcholinesterase activity and plasma butyrylcholinesterase, induces obesity and glucose dysregulation through mechanisms involving altered gut microbiota or increased caloric expenditure. However, weight gain, glucose intolerance, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) also decreased at low CPF doses when test mice were kept thermoneutral. Reported. This indicates that CPF levels consistent with individual non-occupational exposure may promote obesity by preventing diet-induced thermogenesis in BAT.

Other environmental contaminants that may inhibit BAT function

androgen receptor (AR), aryl hydrocarbon receptor (AhR), estrogen receptor (ER), estrogen receptor-related receptor (ERR), thyroid receptor (TR), pregnane X receptor (PXR) and many others of environmental toxins bind to hormone receptors. ) interfered with hormonal effects. These receptors play an important role in controlling thermogenesis of BAT. Environmental toxins include DDT, organochlorines, and vinclozolin, which block androgen receptor-mediated processes, including UCP1 transcription.

Some environmental toxins may influence thermogenesis in BAT by mimicking the action of estrogen. For example, bisphenol A (BPA), the most common industrial chemical used to make plastics, induces weight loss without changing caloric intake. Moreover, maternal exposure to her BPA during pregnancy mimics a weak estrogen agonist, increases her interscapular BAT weight and upregulates her UCP1 expression in female offspring, but Reduces her BAT activity and brown adipogenesis in male offspring.

Overall, the findings of this study highlight that certain environmental contaminants may inhibit thermogenesis in BAT. Further studies should be performed at various doses in the BAT cell line to assess this potential and provide more precise human translatability.