Effects of differential regional PM2.5 induced hepatic steatosis and underlying mechanism

Zhipeng Yan; Shuyue Li; Rui Chen; Haohan Xie; Meiqiong Wu; Nan Nan; Qisong Xing; Yang Yun; Guohua Qin; Nan Sang

doi:10.1016/j.envpol.2023.121220

Effects of differential regional PM_2.5 induced hepatic steatosis and underlying mechanism

Environ Pollut. 2023 Apr 15:323:121220. doi: 10.1016/j.envpol.2023.121220. Epub 2023 Feb 4.

Authors

Zhipeng Yan¹, Shuyue Li¹, Rui Chen², Haohan Xie³, Meiqiong Wu⁴, Nan Nan¹, Qisong Xing¹, Yang Yun¹, Guohua Qin⁵, Nan Sang¹

Affiliations

¹ College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Shanxi, 030006, PR China.
² Beijing Key Laboratory of Occupational Safety and Health, Institute of Urban Safety and Environmental Science, Beijing Academy of Science and Technology, Beijing, 100054, PR China; Beijing City University, Beijing, 11418, PR China.
³ Beijing Key Laboratory of Occupational Safety and Health, Institute of Urban Safety and Environmental Science, Beijing Academy of Science and Technology, Beijing, 100054, PR China.
⁴ College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Shanxi, 030006, PR China; School of Public Health, Shanxi Medical University, Shanxi, 030001, PR China.
⁵ College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Shanxi, 030006, PR China. Electronic address: qinguojua@sxu.edu.cn.

PMID: 36746292
DOI: 10.1016/j.envpol.2023.121220

Abstract

Emerging evidence suggests that exposure to PM_2.5 is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM_2.5-induced hepatic steatosis remain to be elucidated. In this study, ten-month-old C57BL/6 female mice were exposed to PM_2.5 from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM_2.5 was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM_2.5 from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM_2.5 exposure. Moreover, Guangzhou PM_2.5-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM_2.5 significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM_2.5 exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM_2.5. This study provides critical information regarding the components of PM_2.5, which cause hepatic steatosis.

Keywords: Critical chemical components; Hepatic steatosis; Metabolomics; PM(2.5).

MeSH terms

Animals
Fatty Acids / metabolism
Female
Linoleic Acid / metabolism
Lipid Metabolism
Liver / metabolism
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / metabolism
Particulate Matter / metabolism
Particulate Matter / toxicity

Substances

Linoleic Acid
oil red O
Fatty Acids
Particulate Matter