PM2.5 exposure aggravates kidney damage by facilitating the lipid metabolism disorder in diabetic mice

PeerJ. 2023 Sep 1:11:e15856. doi: 10.7717/peerj.15856. eCollection 2023.

Abstract

Background: Ambient fine particulate matter ≤ 2.5 µm (PM2.5) air pollution exposure has been identified as a global health threat, the epidemiological evidence suggests that PM2.5 increased the risk of chronic kidney disease (CKD) among the diabetes mellitus (DM) patients. Despite the growing body of research on PM2.5 exposure, there has been limited investigation into its impact on the kidneys and the underlying mechanisms. Past studies have demonstrated that PM2.5 exposure can lead to lipid metabolism disorder, which has been linked to the development and progression of diabetic kidney disease (DKD).

Methods: In this study, db/db mice were exposed to different dosage PM2.5 for 8 weeks. The effect of PM2.5 exposure was analysis by assessment of renal function, pathological staining, immunohistochemical (IHC), quantitative real-time PCR (qPCR) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) based metabolomic analyses.

Results: The increasing of Oil Red staining area and adipose differentiation related protein (ADRP) expression detected by IHC staining indicated more ectopic lipid accumulation in kidney after PM2.5 exposure, and the increasing of SREBP-1 and the declining of ATGL detected by IHC staining and qPCR indicated the disorder of lipid synthesisandlipolysis in DKD mice kidney after PM2.5 exposure. The expressions of high mobility group nucleosome binding protein 1 (HMGN1) and kidney injury molecule 1 (KIM-1) that are associated with kidney damage increased in kidney after PM2.5 exposure. Correlation analysis indicated that there was a relationship between HMGN1-KIM-1 and lipid metabolic markers. In addition, kidneys of mice were analyzed using LC-MS/MS based metabolomic analyses. PM2.5 exposure altered metabolic profiles in the mice kidney, including 50 metabolites. In conclusion the results of this study show that PM2.5 exposure lead to abnormal renal function and further promotes renal injury by disturbance of renal lipid metabolism and alter metabolic profiles.

Keywords: ATGL; Diabetes mellitus; Diabetic kidney disease; Ectopic lipid accumulation; HMGN1; KIM-1; PM2.5; SREBP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Diabetes Mellitus, Experimental*
  • HMGN1 Protein*
  • Kidney
  • Lipid Metabolism
  • Lipid Metabolism Disorders*
  • Lipids
  • Mice
  • Tandem Mass Spectrometry

Substances

  • HMGN1 Protein
  • Lipids

Grants and funding

This work was supported by grants from The Special Fund for Basic Scientific Research Operating of Central Public Welfare Research Institutes, the Chinese Academy of Medical Sciences (2019PT320003), the Guizhou high-level innovative talents program [QKHPTRC(2018)5636-2], the Guizhou Clinical Research Center for Kidney Disease (QKHPTRC[2020]2201), the Science and Technology Fund project of Guizhou Provincial Health Commission in 2020 (gzwkj2020-084), the Science and Technology Fund project of Guizhou Provincial Health Commission in 2021 (gzwkj2021-136), the Youth Fund of Guizhou Provincial People’s Hospital in 2021 (GZSYQN[2021]12), and the Basic Research Plan of Guizhou Province in 2022 (Natural Science Project) (QKH-ZK[2022] General 265). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.