Exposure memory and susceptibility to ambient PM 2.5 : A perspective from hepatic cholesterol and bile acid metabolism.

Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM _2.5 ) is related to the occurrence and development of chronic diseases, such as metabolic diseases. However, whether PM _2.5 has "exposure memory" and how these memories affect chronic disease development like hepatic metabolic homeostasis are unknown. Therefore, we aimed to explore the effects of exposure transition on liver cholesterol and bile acids (BAs) metabolism in mice. In this study, C57BL/6 mice were exposed to concentrated ambient PM _2.5 or filtered air (FA) in a whole-body exposure facility for an initial period of 10 weeks, followed by another 8 weeks of exposure switch (PM _2.5 to FA and FA to PM _2.5 ) comparing to non-switch groups (FA to FA and PM _2.5 to PM _2.5 ), which were finally divided into four groups (FF of FA to FA, PP of PM _2.5 to PM _2.5 , PF of PM _2.5 to FA, and FP of FA to PM _2.5 ). Our results showed no significant difference in food intake, body composition, glucose homeostasis, and lipid metabolism between FA and PM _2.5 groups after the initial exposure before the exposure switch. At the end of the exposure switch, the mice switched from FA to PM _2.5 exposure exhibited a high sensitivity to late-onset PM _2.5 exposure, as indicated by significantly elevated hepatic cholesterol levels and disturbed BAs metabolism. However, the mice switched from PM _2.5 to FA exposure retained a certain memorial effects of previous PM _2.5 exposure in hepatic cholesterol levels, cholesterol metabolism, and BAs metabolism. Furthermore, 18-week PM _2.5 exposure significantly increased hepatic free BAs levels, which were completely reversed by the FA exposure switch. Finally, the changes in small heterodimeric partner (SHP) and nuclear receptor subfamily 5 group A member 2 (LRH1) in response to exposure switch mechanistically explained the above alterations. Therefore, mice switching from PM _2.5 exposure to FA showed only a weak memory of prior PM _2.5 exposure. In contrast, the early FA caused mice to be more susceptible to subsequent PM _2.5 exposure.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)