Effects of Air Pollution and Endocrine Disease

 

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Front Public Health. 2022 Jul 14;10:882569. doi: 10.3389/fpubh.2022.882569

The Physiological Effects of Air Pollution: Particulate Matter, Physiology and Disease

Jack T Pryor 1,2, Lachlan O Cowley 1, Stephanie E Simonds 1,*

Endocrine Disease

The known effects of cigarette smoke on reproductive and thyroid hormones provide indications of the risks associated with PM exposure.

 Cigarette smoke is a risk factor in Graves hypothyroidism and is associated with elevated plasma cortisol, aldosterone, adrenal androgens and impacts female fertility by increasing steroid hormone binding globulin and decreasing circulating free estrogens (83–86). 

Several PM species have been identified as endocrine disrupting chemicals (87).

 In humans PM exposure is linked to insulin resistance, elevated circulating adipokines, hypothyroidism and (mixed) estrogenic effects (88). 

Thyroid hormones triiodothyronine (T3) and thyroxine (T4) regulate metabolic rate, cardiovascular tone and promote growth rate during fetal development and early life (89).

 In humans, PM exposure is associated with decreased plasma T4 both in pregnant women and new-borns, as well as congenital hypothyroidism and reduced infant birth weight (90). 

Black carbon, ammonia, organic matter and nitrate PM species appear to have the strongest links to thyroid dysfunction (91–94). 

Effective insulin signaling is required for glucose homeostasis, and insulin resistance is closely associated with obesity and is a risk factor for the onset of type-2 diabetes (95).

 PM exposure is associated with insulin resistance and non-alcoholic fatty liver disease, driven by oxidative stress and dyslipidaemia (96, 97).

 Together these studies highlight the link between air pollution and metabolic diseases including diabetes. Of >106 chemicals to which gas and oil extraction workers are exposed, 21 have been shown to exert estrogenic, androgenic and/or steroidogenic effects (98).

 Some chemicals identified as impacting endocrine function include benzene, toluene, ethylbenzene xylene, mercury, polychlorinated dibenzodioxins (PBDDs) and several polycyclic aromatic hydrocarbons (PAH) (88, 98, 99).

 Atmospheric sources of PAHs are vehicle emissions and biomass and coal combustion. Low molecular weight PAHs are in gas phase whereas high molecular weight PAHs are bound to the surface of PM (100). PAHs are classed as endocrine disrupting compounds and have been found to both increase and decrease estrogen receptor mRNA expression and function (REF). Estrogenic dysfunction has been shown to be both direct at estrogen receptors and indirect via aryl hydrocarbon receptor (AhR) signaling (101, 102). 

PBDDs also exert endocrine effects via AhRs, and preclinical experiments have shown AhR-mediated effects of dioxin exposure to include weight loss, reproductive and developmental toxicity, tumorigenesis and immune system dysfunction (103). 

PM contains many metal elements, some of which interfere with estrogenic signaling by mimicking endogenous estrogens (104). Metalloestrogens include aluminum, selenium, antimony, arsenic (arsenite; NaAsO2), barium, cadmium, chromium, cobalt, copper, lead, mercury, nickel, tin and vanadium (vanadate; V2O5) (16, 104).

Obesity and Diabetes

In humans, the association between PM2.5 exposure and obesity is dependent on age, gender and socioeconomic demographic (105, 106).

 A growing body of evidence indicates that PM2.5 exposure is a risk factor for reduced skeletal muscle mass, obesity, diabetes and hypertension (107–109). 

Long-term PM exposure is associated with a high risk for type 2 diabetes, and road traffic-specific PM is correlated with an elevated risk (110). 

Increased incidence of type-2 diabetes remains when adjusted for age, body mass index (BMI), and socioeconomic status (111, 112). 

PM exposure is associated with higher levels of circulating complement factor 3 (C3c), and women with elevated plasma C3c are more susceptible to diabetes than those with low C3c (112). PM2.5 exposure is associated with a faster decline in insulin sensitivity during childhood and higher BMI by age 18 (113–115). 

The associated between PM exposure and hypertension is greater in overweight and obese children (116). In animal studies, exposure of rats to PM increased chocolate consumption whereas in chow-fed wild-type mice, 10-week PM2.5 exposure increased visceral fat mass, insulin resistance and adipose tissue inflammation (117, 118). In mice, short-term PM exposure increased food intake, fat mass and UCP-1 expression in brown adipose tissue (119). PM exposure also induced hypothalamic inflammation indicated by increased microglia density, increased toll-like receptor-4 and elevated inhibitory nuclear factor-kappa-B-kinase-epsilon expression (119). After 12 weeks of PM exposure, mice exhibited increased food intake and elevated fat mass and had lower energy expenditure. Mice had elevated levels of plasma leptin and insulin and increased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) indicators of insulin resistance (119). This same study also revealed that PM exposure decreased hypothalamic satiety markers, including reduced levels of phosphorylated STAT 3, and diminished proopiomelanocortin expression (119).

PM exposure to mice was found to induce hepatic oxidative stress, inflammation, negatively affect glucose tolerance and induce insulin resistance (96, 120). Interestingly PM exposure has been found to increase hepatic triacylglycerols, free fatty acids and cholesterol levels in female but not in male mice (96). In addition to insulin resistance, PM exposure has been shown to exert toxic effects directly on the pancreas (121). In a streptozotocin-induced mouse model of type-1 diabetes, PM from diesel exhaust fumes exacerbated pancreatic cell vacuolation and islet cell apoptosis, increased pancreatic amylase activity, increased expression of oxidative stress markers 8-isoprostane and superoxide dismutase and reduced levels of the antioxidant glutathione peroxidase (121). In a rat model of gestational diabetes PM exposure induced maternal pancreatic inflammation indicated by diminished pancreatic glucose transporter-2 expression (122).