Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice

Autor: He Tian, Rucheng Chen, Lu Zhang, Guanghou Shui, Kezhong Zhang, Ran Li, Sin Man Lam, Weijia Gu, Junyao Zhu, Qinghua Sun, Lung Chi Chen, Qing Sun, Cuiqing Liu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Apolipoprotein B
Health
Toxicology and Mutagenesis
010501 environmental sciences
Toxicology
01 natural sciences
chemistry.chemical_compound
Mice
Random Allocation
Gonadal Steroid Hormones
0303 health sciences
Air Pollutants
Sex Characteristics
biology
Chemistry
Metabolic disorder
General Medicine
Lipids
Lipids accumulation
Liver
Female
medicine.medical_specialty
lcsh:Industrial hygiene. Industrial welfare
Air pollution
complex mixtures
03 medical and health sciences
Insulin resistance
lcsh:RA1190-1270
Internal medicine
Lipidomics
medicine
Animals
Particle Size
lcsh:Toxicology. Poisons
030304 developmental biology
0105 earth and related environmental sciences
Triglyceride transport
Cholesterol
Research
Metabolism
medicine.disease
Sex difference
Lipid Metabolism
Mice
Inbred C57BL
Endocrinology
biology.protein
Particulate Matter
lcsh:HD7260-7780.8
Hormone
Zdroj: Particle and Fibre Toxicology
Particle and Fibre Toxicology, Vol 17, Iss 1, Pp 1-14 (2020)
ISSN: 1743-8977
Popis: Background & aims Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. Methods Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. Results Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. Conclusions Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.
Databáze: OpenAIRE
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