Endocrine impacts of long-term high temperature housing: interactive influence of subchronic wild-fire smoke exposure and high cholesterol diet in male rats
Citation:
Kodavanti, U., D. Alewel, M. Schladweiler, R. Grindstaff, P. Evansky, D. Davies, M. Monsees, W. Williams, AND T. Jackson. Endocrine impacts of long-term high temperature housing: interactive influence of subchronic wild-fire smoke exposure and high cholesterol diet in male rats. Society of Toxicology, Salt Lake City, UT, March 10 - 14, 2024.
Impact/Purpose:
This study examines the interactive contribution of climate stressors such as high temperature, wildfire smoke exposure and non-chemical dietary stressors on health through alteration in the metabolic and reproductive hormones.
Description:
Basal increases in ambient temperature and regional temperature spikes are associated with changes in weather patterns, increases in wildfires and other natural disasters. This pattern of climate change directly or indirectly impacts human health and lifestyle, especially in vulnerable communities. We embarked on investigating how increased temperature might impact the health from other stressors such as wildfire smoke exposure and/or unhealthy diet containing high levels of cholesterol. The goal of this part of the project was to determine how endocrine regulation of two fundamental survival processes, such as metabolism and reproduction, might be impacted by high temperature, when animals are already experiencing other life stressors such as exposure to wildfire smoke, and the availability/consumption of unhealthy diet. Male Wistar Kyoto rats (4-week-old) were housed at room temperature (RT, 22 oC) or high temperature (HT, slightly above thermoneutrality for rats; 31 oC) and began to receive either normal rat chow (ND; TD.220163 2% cellulose diet), or chow supplemented with 2% cholesterol (HCD; TD.220164 2% cholesterol diet). In the following weeks, rats were exposed to filtered air or air mixed with tube furnace-generated eucalyptus whole wood smoke (wildfire eucalyptus smoke; WFES; ~7 mg/m3 particulate mass and <20 ppm carbon monoxide [GI1] x 1hr/d x 1d/week) for 12-13 weeks while on respective temperatures or diets. Two days after the 12th or 13th exposure, serum levels hormones and metabolites were assessed. As presented previously, there were significant interactive impacts of temperature, WFES, and cholesterol diet on serum levels of glucose and lipid metabolites including cholesterols. Here we noted that primary metabolic hormones involved in regulating physiological processes were dramatically impacted by HT housing. Insulin levels were significantly lower in HT animals regardless of WFES or HCD, where HCD animals exposed to WFES and housed at HT had the highest drop in insulin. Interestingly, HT reduced circulating glucose. The levels of circulating Leptin also were significantly lower in HT animals regardless of other stressors. Surprisingly, HCD at RT also reduced leptin levels with no impact of WFES. The increases in levels of circulating thyroid stimulating hormone (TSH) in HT were associated with marked decreases in T3 and T4 in all HT animals. In RT animals, HCD also reduced T3 and T4 levels without having much influence of WFES. HT also had significant interactive effects with other stressors on sex hormones. Luteinizing hormone, involved in producing testosterone, was lower in all animals housed at HT and also in HCD animals housed at RT and exposed to WFES. Prolactin involved in immune regulation, metabolism and reproduction was again lower in all animals housed at HT regardless of stress condition; and in all WFES-exposed animals fed ND or HCD. This pattern of change by HT in all metabotropic and reproductive hormones including those produced in the anterior pituitary gland and also other stressors demonstrates interactive biological mechanisms. The long-term exposure to higher ambient temperature could have profound effects on basic metabolic homeostatic function and might impair reproductive function. Whether the hormone change phenotype is due to growth retardation as HT animals gained ~30% less weight than RT, or could be linked to long-term adaptation remains to be investigated. Nevertheless, other environmental stressors such as exposure to wildland fire smoke or unhealthy dietary habits selectively exacerbated some of the hormonal changes observed in animals living at HT. The hormonal changes observed in the present study indicate involvement of neuroendocrine mechanisms in modulating response to high temperature, smoke inhalation and unhealthy cholesterol-rich diets. (This abstract does not reflect EPA policy).