Airborne PM2.5 pollution: A double-edged sword modulating hepatic lipid metabolism in middle-aged male mice. (1st May 2023)

• Record Type: Journal Article
• Authors: Hu, Renjie; Zhang, Lu; Qin, Li; Ding, Hao; Li, Ran; Gu, Weijia; Chen, Rucheng; Zhang, Yunhui; Rajagoplan, Sanjay; Zhang, Kezhong; Sun, Qinghua; Liu, Cuiqing
• Is Part Of: Environmental pollution. Volume 324(2023)
• Publication Date: 2023-05-01
• Subjects: Fine particulate matter -- Middle-aged mice -- Lipid metabolism -- Transcriptomics -- Lipidomics; Acaa1b acetyl-CoA acyltransferase 1b -- Acc 1/2 acetyl-CoA carboxylase 1/2 -- Acly ATP citrate lyase -- Acot1-4 acyl-CoA thioesterase 1–4 -- Acox2 acyl-CoA oxidase 2 -- Ascl1 acyl-CoA synthetase long-chain family member 1 -- Agpat2 1-acylglycerol-3-phosphate O-acyltransferase 2 -- Akr1d1 steroid 5β-reductase -- Aldh3a2 aldehyde dehydrogenase 3 family member a2 -- Apoa5 apolipoprotein a5 -- Apob apolipoprotein b -- Atgl adipose triglyceride lipase -- C1P ceramide 1-phosphate -- Cat catalase -- CDP-DAG CDP-diacylglycerol -- Cds2 CDP-diacylglycerol synthase -- Cept1 choline/ethanolaminephosphotransferase 1 -- Cer ceramide -- CHO cholesterol -- CL cardiolipin -- Cpt1a carnitine palmitoyl-transferase 1a -- Cyp4a12b cytochrome P450 -- family 4 subfamily a -- polypeptide 12b Cyp4a14 -- cytochrome P450 family 4 -- subfamily a polypeptide 14 -- Cyp7a1 cholesterol 7α-hydroxylase -- Cyp7b1 cholesterol hydroxylases -- Cyp8b1 sterol 12α-hydroxylase -- Cyp27a1 sterol-27 hydroxylase -- DAG diacylglycerol -- Dgat1/2 diacylglycerol acyltransferase 1/2 -- DHAP dihydroxyacetone phosphate -- EC elemental carbon -- Elovl3 elongase of very long chain fatty acids-3 -- FA filtered air -- Fabp1/2/5 fatty acid-binding protein 1/2/5 -- Fads 2 fatty acid desaturase 2 -- Fxr farnesoid X receptor -- G3P glycerol-3-phosphate -- GlcCer glucosylceramide -- Gpam/Gpat3/4 Glycerol-3-phosphate acyltransferase 1/3/4 -- GO gene ontology -- Gpd1 glycerol-3-phosphate dehydrogenase 1 -- Gpx 1 glutathione peroxidase 1 -- GSEA gene set enrichment analysis -- GSL glycosphingolipid -- GTT glucose tolerance testing -- Ho-1 heme oxygenase-1 -- HOMA-IR homeostasis model assessment of insulin resistance -- Hsd3b7 3β-hydroxy-delta(5)-C(27)-steroid oxidoreductase -- Hsd17b4 17β-hydroxysteroid dehydrogenase type 4 -- Hsl hormone-sensitive lipase -- KEGG kyoto encyclopedia of genes and genomes -- LPC lyso-phosphatidylcholine -- LPE lyso-phosphatidylethanolamine -- Lpl lipoprotein lipase -- Mttp microsomal triglyceride transfer protein -- OC organic carbon -- Pcyt2 CTP:phosphoethanolamine cytidylyltransferase 2 -- PA phosphatidic acid -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- Pex11a peroxisomal biogenesis factor 11α -- PG phosphatidylglycerol -- PI phosphatidylinositol -- Pla2g6 phospholipase A2 group VI -- Plin5 perilipin 5 -- Plpp2 phospholipid phosphatase 2 -- PM2.5 fine particulate matter -- Pparα/γ peroxisome-proliferator activated receptor α/γ -- PS phosphatidylserine -- S1P sphingosine 1-phosphate -- Scd1 stearoyl-CoA desaturase 1 -- SM sphingomyelin -- Smpd3 sphingomyelin phosphodiesterase 3 -- Sod 1/2 superoxide dismutase 1/2 -- TG triglyceride -- Ugcg UDP—glucose ceramide glycosyltransferase -- Vlcad very long chain acyl-CoA dehydrogenase; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2023.121347
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Emerging evidence suggests that exposure to airborne fine particulate matter (PM2.5 ) is closely related to disturbances in hepatic lipid metabolism. However, no systematic study assessed the age vulnerability in effects of PM2.5 exposure on metabolism, and the potential mechanisms remain unknown. This study aimed to investigate the metabolic susceptibility of different life stages to PM2.5 exposure, and to evaluate the underlying molecular mechanisms. Male C57BL/6 mice at three life phases (young, adult, and middle-aged) were exposed simultaneously to concentrated ambient PM2.5 or filtered air (FA) for 8 weeks using a whole-body inhalational exposure system. The average daily PM2.5 concentrations to which mice were actually exposed were 90.71 ± 7.99 μg/m 3 . The body weight, total food utilization, body composition, glucose metabolic homeostasis of the mice were evaluated. At euthanasia, serum and liver samples were collected to measure lipid profiles and hepatic function. H&E and Oil Red O staining were used to assess the liver cellular structure and hepatic lipid deposition. Transcriptomics and lipidomics were performed to determine the differentially expressed genes and lipid metabolites in the liver. Quantitative RT-PCR and immunoblots were performed to verify the transcriptomics and explore the mechanism for metabolic susceptibility. PM2.5 exposure led to reductions in body weight gain, total food utilization, and fat mass in middle-aged mice but not in young or adults. Exposure to PM2.5 reduced hepatic lipid deposition by enhancing lipolysis and inhibiting the glycerol-3-phosphate (G3P) pathway of hepatic lipogenesis. Furthermore, PM2.5 exposure attenuated hepatic fatty acid metabolism and primary bile acid biosynthesis. Finally, PM2.5 exposure dysregulated hepatic phospholipid metabolism, as evidenced by increased glycerophospholipid synthesis and disturbed sphingolipid metabolism. Therefore, middle-aged male mice were more vulnerable to PM2.5 exposure with double-edged effects, improved metabolism and hepatic TG accumulation but inhibited hepatic fatty acid and bile acid metabolism and dysregulated phospholipid metabolism. Graphical abstract: Image 1 Highlights: Middle-aged male mice were more vulnerable to PM2.5 exposure. PM2.5 exposure had double-edged effects on metabolism of middle-aged mice. PM2.5 exposure reduced hepatic TG deposition in middle-aged mice. PM2.5 exposure inhibited hepatic FA and bile acid metabolism in middle-aged mice. PM2.5 exposure dysregulated hepatic phospholipid metabolism in middle-aged mice.