PM2.5 induced liver lipid metabolic disorders in C57BL/6J mice

Front Endocrinol (Lausanne). 2023 Sep 14:14:1212291. doi: 10.3389/fendo.2023.1212291. eCollection 2023.

Abstract

PM2.5 can cause adverse health effects via several pathways, such as inducing pulmonary and systemic inflammation, penetration into circulation, and activation of the autonomic nervous system. In particular, the impact of PM2.5 exposure on the liver, which plays an important role in metabolism and detoxification to maintain internal environment homeostasis, is getting more attention in recent years. In the present study, C57BL/6J mice were randomly assigned and treated with PM2.5 suspension and PBS solution for 8 weeks. Then, hepatic tissue was prepared and identified by metabolomics analysis and transcriptomics analysis. PM2.5 exposure can cause extensive metabolic disturbances, particularly in lipid and amino acids metabolic dysregulation.128 differential expression metabolites (DEMs) and 502 differently expressed genes (DEGs) between the PM2.5 exposure group and control group were detected. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in two disease pathways, non-alcoholic fatty liver disease (NAFLD) and type II diabetes mellitus (T2DM), and three signaling pathways, which are TGF-beta signaling, AMPK signaling, and mTOR signaling. Besides, further detection of acylcarnitine levels revealed accumulation in liver tissue, which caused restricted lipid consumption. Furthermore, lipid droplet accumulation in the liver was confirmed by Oil Red O staining, suggesting hepatic steatosis. Moreover, the aberrant expression of three key transcription factors revealed the potential regulatory effects in lipid metabolic disorders, the peroxisomal proliferative agent-activated receptors (PPARs) including PPARα and PPARγ is inhibited, and the activated sterol regulator-binding protein 1 (SREBP1) is overexpressed. Our results provide a novel molecular and genetic basis for a better understanding of the mechanisms of PM2.5 exposure-induced hepatic metabolic diseases, especially in lipid metabolism.

Keywords: PPARα; PPARγ; SREBP1; hepatic steatosis; metabolomics; particulate matter; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / complications
  • Lipid Metabolism Disorders* / genetics
  • Lipids
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / etiology
  • Particulate Matter / toxicity

Substances

  • Particulate Matter
  • Lipids

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant No. 21777099, XD), SJTU Public Health School Local High-level University Achievement-oriented Top-notch Cultivation Programme for Undergraduate Students (Grant No. 18ZYGW12), and Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.