Exercise ameliorates fine particulate matter-induced metabolic damage through the SIRT1/AMPKα/PGC1-α/NRF1 signaling pathway.

Air pollution, particularly fine particulate matter (PM2.5), poses a major threat to human health. Exercise has long been recognized as a beneficial way to maintain physical health. However, there is limited research on whether exercise can mitigate the damage caused by PM2.5 exposure. In this study, the mice were exercised on the IITC treadmill for 1 h per day, then exposed to concentrated PM2.5 for 8 h. After 2, 4 and 6-month exercise and PM2.5 exposure, the glucose tolerance and insulin tolerance were determined. Meanwhile, the corresponding indicators in epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) and skeletal muscle were detected. The results indicated that PM2.5 exposure significantly increased insulin resistance (IR), while exercise effectively attenuated this response. The observations of muscle, BAT and eWAT by transmission electron microscopy (TEM) showed that PM2.5 significantly reduced the number of mitochondria in all of the three tissues mentioned above, and decreased the mitochondrial area in skeletal muscle and BAT. Exercise reversed the changes in mitochondrial area in all of the three tissues, but had no effect on the reduction of mitochondrial number in skeletal muscle. At 2 months, the expressions of Mfn2, Mfn1, OPA1, Drp1 and Fis1 in eWAT of the PM mice showed no significant changes when compared with the corresponding FA mice. However, at 4 months and 6 months, the expression levels of these genes in PM mice were higher than those in the FA mice in skeletal muscle. Exercise intervention significantly reduced the upregulation of these genes induced by PM exposure. The study indicated that PM2.5 may impact mitochondrial biogenesis and dynamics by inhibiting the SIRT1/AMPKα/PGC1-α/NRF1 pathway, which further lead to IR, glucose and lipid disorders. However, exercise might alleviate the damages caused by PM2.5 exposure.

Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis.

BACKGROUND: The growing consensus links exposure to fine particulate matter (PM2.5) with an increased risk of respiratory diseases. However, little is known about the additional effects of particulate matter on brainstem function in allergic rhinitis (AR). Furthermore, it is unknown to what extent the PM2.5-induced effects in the brainstem affect the inflammatory response in AR. This study aimed to determine the effects, mechanisms and consequences of brainstem neural activity altered by allergenic stimulation and PM2.5 exposure. METHODS: Using an AR model of ovalbumin (OVA) elicitation and whole-body PM2.5 exposure, the metabolic profile of the brainstem post-allergen stimulation was characterized through in vivo proton magnetic resonance imaging (1H-MRS). Then, the transient receptor potential vanilloid-1 (TRPV1) neuronal expression and sensitivity in the trigeminal nerve in AR were investigated. The link between TRPV1 expression and brainstem differential metabolites was also determined. Finally, we evaluated the mediating effects of brainstem metabolites and the consequences in the brain-spleen axis in the inflammatory response of AR. RESULTS: Exposure to allergens and PM2.5 led to changes in the metabolic profiles of the brainstem, particularly affecting levels of glutamine (Gln) and glutamate (Glu). This exposure also increased the expression and sensitivity of TRPV1+ neurons in the trigeminal nerve, with the levels of TRPV1 expression closely linked to the brainstem metabolism of Glu and Gln. Moreover, allergens increased the activity of p38, while PM2.5 led to the phosphorylation of p38 and ERK, resulting in the upregulation of TRPV1 expression. The brainstem metabolites Glu and Gln were found to partially mediate the impact of TRPV1 on AR inflammation, which was supported by the presence of pro-inflammatory changes in the brain-spleen axis. CONCLUSION: Brainstem metabolites are altered under allergen stimulation and additional PM2.5 exposure in AR via sensitization of the trigeminal nerve, which exacerbates the inflammatory response via the brain-splenic axis.