Citation:

Jackson, T., D. Alewel, Mette C Schladweiler, P. Evansky, D. Davies, M. Monsees, M. Hazari, A. Farraj, AND U. Kodavanti. Lifestyle and climate factors interact with wildfire-related air pollution to worsen neuroendocrine and cardiometabolic function. Society of Toxicology, Nashville, TN, March 19 - 23, 2023.

Impact/Purpose:

This study shows how climate factors, such as exposure to high ambient temperature, wildfire smoke exposure  and high cholesterol diet, over a 3-month period interactively alter to cause cardiometabolic changes in a relent model. The data show effects of individual stressor and interactive effects of all these stressors with high ambient temperature causing complex interactive effects on multiple phenotypic markers and functional impairments. 

Description:

Climate scenarios predict more frequent and longer-lasting heatwaves alongside increased ambient particulate levels from widespread wildfires. These conditions are predicted to exacerbate cardiometabolic disorders, especially in vulnerable populations. We hypothesized that stress caused by high-temperature housing (HT), unhealthy high-cholesterol diet (HCD), and episodic subchronic wildfire-related eucalyptus smoke exposure (WFES) would interact to disrupt cardiometabolic homeostasis. Male Wistar-Kyoto rats (4-week-old) housed at standard housing conditions (~22°C) or HT, (~31°C) just above temperatures historically characterized as thermoneutral for rats, for 13 weeks received either normal (ND) or 2% cholesterol-supplemented diet (HCD) and were exposed to either filtered air or WFES (~7 mg/m3 x 1hr/d x 1d/week x 13 weeks). In-life testing of metabolic and cardiovascular physiology were performed during exposure periods, while tissue and ex vivo vascular assessment were performed at necropsy. Rats at HT had substantial reductions (>30%) in body weight gain and increased lean mass compared to 22°C (RT) housed rats regardless of diet. HCD increased serum cholesterol (driven by increases in LDL) and caused fatty livers in rats at RT or HT; in HT rats, the overall cholesterol increase was mitigated due to a concomitant reduction in HDL that was irrespective of diet. Glucose homeostasis was strikingly disrupted by HCD and/or WFES, and these effects were dramatically modified by HT housing. Glucose tolerance testing (GTT) revealed that, in general, HT rats had lower basal glucose and increased glucose clearance compared to RT. The HCD- and WFES-induced glucose intolerance noted in RT rats was less remarkable in HT rats. In all groups, WFES-exposed rats exhibited decreased glucose clearance. Insulin tolerance testing revealed that WFES or HCD effects on glucose clearance were not due to insulin resistance. Pyruvate tolerance testing revealed that HCD decreased gluconeogenesis, and that this effect was exacerbated in HT rats. The disruptions in glucose homeostasis indicate that the observed glucose intolerance is likely due to insulin insufficiency, an effect often observed during subchronic exposure to stress. Marked interactive cardiovascular effects of HT, WFES, and HCD were noted along with alterations in blood clinical biomarkers of coagulation. HT rats showed evidence of thrombocytopenia alongside increased platelet volume, indicating disruption of hematopoiesis and blood chemistry. Thrombocytopenia effects of HT in HCD were exacerbated in WFES-exposed rats. Atherogenic vascular effects of HCD and WFES, tested using an ex vivo aortic ring bath and cardiovascular ultrasound were again modified by HT. At RT, HCD or WFES individually amplified aortic vasoconstriction and minimized vasorelaxation induced by respective agonists (HCD>WFES), with greater cumulative effects observed with combined HCD and WFES. However, these vascular effects of HCD and/or WFES were mitigated in animals at HT. These clinically relevant data demonstrate that HT reduced growth and exacerbated WFES and/or HCD-associated platelet alterations while mitigating glucose and HDL metabolic effects together with compensating for cardiovascular physiological responses associated with both these stressors. Thus, lifestyle factors (e.g. unhealthy diet) can interact with climate-induced increases in temperature and/or air pollution exposures to induce cardiometabolic disruption and exacerbate chronic disease outcomes.

Record Details: