| Background:Atmospheric pollution is considered as one of the greatest threats to human health and can cause damage to multiple tissues of the organism.Fine particulate matter(PM2.5)is more harmful due to its small diameter and large surface area.Obesity has become a worldwide epidemic and an urgent health problem,which can cause a variety of metabolic diseases and system damage,shorten life expectancy and endanger human health.In recent years,more and more epidemiological studies have shown that obesity is closely related to air pollution.Especially,the association between childhood obesity and air pollution has attracted more attention.The occurrence of overweight and obesity is often accompanied by disorders of lipid metabolism.Animal experiments have shown that the disruption of lipid metabolism caused by PM2.5 is more significant in female animals.As sites of energy production,mitochondria are essential in maintaining lipid metabolic homeostasis.Objective:Therefore,young mice were exposed to PM2.5 using the real-ambient exposure system that we previously established in Shijiazhuang city,aiming to investigate the disruption of lipid metabolism due to PM2.5 and related mechanisms,and to provide deeper insights into the harm of PM2.5 on adolescents.Methods:The young mice were contaminated using a real environment PM exposure system in Shijiazhuang,Hebei,China.After 4 and 8 weeks of exposure,respectively,gonadal adipose tissue(g WAT),subcutaneous adipose tissue(s WAT),liver and serum were collected from each group of mice and weighed for analysis.The effects of PM2.5exposure on each tissue structure were evaluated by observing the pathological structures of liver and adipose tissue using the H&E method.Total RNA was extracted from liver and adipose tissue,and the relative m RNA expression levels of fatty acid synthesis and fatty acid oxidation-related genes were measured by real-time fluorescence quantitative PCR assay.The levels of very low density lipoprotein(VLDL)and free fatty acids(FFA)in liver and serum were measured by enzyme-linked immunosorbent assay(ELISA),respectively.Thus,the phenomenon that PM2.5 exposure affects the homeostasis of lipid metabolism was elucidated.Perform lipidomic,metabolomic and transcriptomic analyses of adipose,liver and serum,respectively,to comprehensively analyze alterations of key metabolites and pathways in liver and adipose tissue during physiological processes and predict biomarkers of disease.To clarify the effects of PM2.5 exposure on lipid metabolism.Total DNA was extracted from liver and adipose tissues,and the levels of 18 S and D-Loop were detected by qPCR to calculate the mitochondrial copy number(mt DNA copy number)levels in the tissues.qPCR experiments were performed to detect the relative expression levels of key mitochondrial regulatory genes.Immunohistochemical and immunofluorescence analyses were performed to further validate the content of relevant proteins regulating mitochondrial activity,and finally to reveal the mechanism of mitochondrial action in causing disorders of lipid metabolism under PM2.5 exposure conditions.Results:Compared to the control group,a significant increase in the weight of g WAT and s WAT was found after 8 weeks of staining,and H&E staining showed a significant increase in adipocytes.There was a significant increase in serum VLDL after 8 weeks of exposure.This suggests that PM2.5 exposure causes expansion of adipose tissue and induces changes in lipid metabolites.Lipidomic analysis screened for multiple differential metabolites,with significant changes in gonadal adipose tissue g WAT and subcutaneous adipose tissue s WAT for 18 and 9 lipid metabolites including triglycerides within(TG),respectively.Metabolomics revealed significant downregulation of the unsaturated fatty acid buty2-enoic acid in the liver.Liver transcriptomics showed significant upregulation of fatty acid metabolism,fatty acid prolongation,and fatty acid degradation pathways.Further qPCR validation of related genes revealed that the expression levels of fatty acid oxidation genes,represented by PPARα,Hadh and Acads,were significantly decreased in liver,while the expression of fatty acid synthesis genes,FAS and SCD1,were significantly increased in white adipose tissue.Further immunohistochemical and immunofluorescence analyses revealed that the protein levels of carnitine palmitoyltransferase-1(CPT1),carnitine palmitoyltransferase-1(CPT2),and peroxisome proliferator-activated receptor-γcoactivator-1α(PGC1α)were significantly increased in the liver,and the protein expression of CPT2 and PGC1α was significantly enhanced in subcutaneous adipose tissue.These findings suggest that mitochondrial activity is increased in liver and adipose tissue during PM2.5 exposure.Conclusions:Taken together,our research investigated the hypotrophy of adipose tissue in young mice,based on multi-omics analysis,the occurrence of lipid metabolism disorders in adipose tissue and liver caused by PM2.5 was more clearly identified and further revealed the alteration of mitochondrial activity in each tissue after the end of exposure.The present study further extends our understanding about the health effects of exposure to PM2.5 at an early age and provide evidence-based support for epidemiological studies on air pollution increasing the prevalence of overweight or obesity in children and adolescents. |
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