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Effect of early particulate air pollution exposure on obesity in mice: role of p47phox.

ABSTRACT: To evaluate the role of early-life exposure to airborne fine particulate matter (diameter, <2.5 ?m [PM(2.5)]) pollution on metabolic parameters, inflammation, and adiposity; and to investigate the involvement of oxidative stress pathways in the development of metabolic abnormalities.PM(2.5) inhalation exposure (6 h/d, 5 d/wk) was performed in C57BL/6 mice (wild type) and mice deficient in the cytosolic subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47(phox) (p47(phox-/-)) beginning at the age of 3 weeks for a duration of 10 weeks. Both groups were simultaneously fed a normal diet or a high-fat diet for 10 weeks. PM(2.5)-exposed C57BL/6 mice fed a normal diet exhibited metabolic abnormalities after exposure to PM(2.5) or FA for 10 weeks. Consistent with insulin resistance, these abnormalities included enlarged subcutaneous and visceral fat contents, increased macrophage infiltration in visceral adipose tissue, and vascular dysfunction. Ex vivo-labeled and infused monocytes demonstrated increased adherence in the microcirculation of normal diet- or high-fat diet-fed PM(2.5)-exposed mice. p47(phox-/-) mice exhibited an improvement in parameters of insulin resistance, vascular function, and visceral inflammation in response to PM(2.5).Early-life exposure to high levels of PM(2.5) is a risk factor for subsequent development of insulin resistance, adiposity, and inflammation. Reactive oxygen species generation by NADPH oxidase appears to mediate this risk.

SUBMITTER: Xu X

PROVIDER: S-EPMC3065931 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Effect of early particulate air pollution exposure on obesity in mice: role of p47phox.

Xu Xiaohua X Yavar Zubin Z Verdin Matt M Ying Zhekang Z Mihai Georgeta G Kampfrath Thomas T Wang Aixia A Zhong Mianhua M Lippmann Morton M Chen Lung-Chi LC Rajagopalan Sanjay S Sun Qinghua Q

Arteriosclerosis, thrombosis, and vascular biology 20100923 12

<h4>Objective</h4>To evaluate the role of early-life exposure to airborne fine particulate matter (diameter, <2.5 μm [PM(2.5)]) pollution on metabolic parameters, inflammation, and adiposity; and to investigate the involvement of oxidative stress pathways in the development of metabolic abnormalities.<h4>Methods and results</h4>PM(2.5) inhalation exposure (6 h/d, 5 d/wk) was performed in C57BL/6 mice (wild type) and mice deficient in the cytosolic subunit of the nicotinamide adenine dinucleotide ...[more]

PMID: 20864666

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Project description:BackgroundDespite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent.ObjectivesWe sought to test the hypothesis that airborne particulate exposures during early-phase spermatogenesis will have a differential impact on spermatogenic formation compared to late-phase exposures, using an individualized model of exposure to particulate matter ≤ 2.5 µm and ≤ 10 µm (PM2.5 and PM10, respectively).MethodsFrom an original cohort of 183 couples, we conducted a retrospective analysis of 130 healthy males seeking to become parents, using spermatogenesis-relevant exposure windows of 77-34 days and 37-0 days prior to semen collection to encompass sperm development stages of mitosis/meiosis and spermiogenesis, respectively. Individualized residential exposure to PM2.5 and PM10 was estimated by selecting multiple air pollution sensors within the same geographic air basin as participants and employing inverse distance weighting to calculate mean daily exposure levels. We used multiple logistic regression to assess the association between pollution, temperature, and dichotomized World Health Organization semen parameters.ResultsDuring the early phase of spermatogenesis, air pollution exposure is associated with 1.52 (95% CI: 1.04-2.32) times greater odds of < 30% normal heads per 1-unit increase in IQR for PM2.5. In the late phase of spermatogenesis, air pollution exposure is associated with 0.35 (95% CI: 0.10-0.74) times greater odds of semen concentration < 15 million/mL per 1-unit increase in IQR for PM2.5, and 0.28 (95% CI: 0.07-0.72) for PM10.ConclusionParticulate exposure has a differential and more deleterious impact on sperm during early-phase spermatogenesis than late-phase.

Project description:BackgroundAir pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression.ObjectivesWe sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development.MethodsWe exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.ResultsWe observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males.ConclusionsWe observed brain region- and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.

Project description:BackgroundChronic exposure to particulate air pollution may accelerate cognitive decline in older adults, although data on this association are limited. Our objective was to examine long-term exposure to particulate matter (PM) air pollution, both coarse ([PM 2.5-10 μm in diameter [PM(2.5-10)]) and fine (PM <2.5 μm in diameter [PM(2.5)]), in relation to cognitive decline.MethodsThe study population comprised the Nurses' Health Study Cognitive Cohort, which included 19,409 US women aged 70 to 81 years. We used geographic information system-based spatiotemporal smoothing models to estimate recent (1 month) and long-term (7-14 years) exposures to PM(2.5-10), and PM(2.5) preceding baseline cognitive testing (1995-2001) of participants residing in the contiguous United States. We used generalized estimating equation regression to estimate differences in the rate of cognitive decline across levels of PM(2.5-10) and PM(2.5) exposures. The main outcome measure was cognition, via validated telephone assessments, administered 3 times at approximately 2-year intervals, including tests of general cognition, verbal memory, category fluency, working memory, and attention.ResultsHigher levels of long-term exposure to both PM(2.5-10) and PM(2.5) were associated with significantly faster cognitive decline. Two-year decline on a global score was 0.020 (95% CI, -0.032 to -0.008) standard units worse per 10 μg/m(3) increment in PM(2.5-10) exposure and 0.018 (95% CI, -0.035 to -0.002) units worse per 10 μg/m(3) increment in PM(2.5) exposure. These differences in cognitive trajectory were similar to those between women in our cohort who were approximately 2 years apart in age, indicating that the effect of a 10-μg/m(3) increment in long-term PM exposure is cognitively equivalent to aging by approximately 2 years.ConclusionLong-term exposure to PM(2.5-10) and PM(2.5) at levels typically experienced by many individuals in the United States is associated with significantly worse cognitive decline in older women.

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Effect of early particulate air pollution exposure on obesity in mice: role of p47phox.

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Effect of early particulate air pollution exposure on obesity in mice: role of p47phox.

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