Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time. Environmental factors are increasingly found to be associated with the development of obesity. To investigate if air pollution exposure contributes to adiposity and inflammation in adipose tissues that induces macro- and microvascular dysfunction, we hypothesize that exposure to fine particulate matter (PM2.5) pollution induces inflammation in both white (visceral) and brown (peri-aortic) adipose tissue, increases accumulation of white fat mass, and potentiates vascular dysfunction via monocyte/macrophage dependent reactive oxygen species (ROS) of NAD(P)H oxidase pathway. To achieve this goal, we first explore the impact of PM2.5 exposure on white and brown adipocytes and associated vascular dysfunction in transgenic mice expressing yellow fluorescent protein (YFP) under the control of monocyte-macrophage specific promoter (c-fms, c-fmsYFP) to ambient PM2.5 or filtered air (control) in a whole body exposure system ?Ohio?s Air Pollution Exposure System for the Interrogation of Systemic Effects (OASIS)-1? up to 24 weeks. Magnetic resonance imaging (MRI) to evaluate body fat mass/distribution, integrated positron-emission tomography and computed tomography (microPET-CT) to evaluate the activity of brown adipose tissue, tissue histological examination to assess mitochondria content, adipocyte hyperplasia and hypertrophy, and vascular growth in the fat tissues, intravital microscopy to illustrate microvascular function and leukocyte trafficking, and myograph to investigate macrovascular function will be performed. PM2.5 with Nickel or PM2.5 with vanadium will be compared to PM2.5 exposure alone to evaluate differences in biological responses. We then investigate the functional changes in adipocytes and macrophage activation in white and brown adipose tissues on early adipocyte progenitor cell (APC), in vivo adipogenesis, newly recruited macrophages in adipose tissues, mitochondria content, uncoupling protein (UCP)1 expression, monocyte migration, and monocyte M1/M2 gene expression. We finally study if PM2.5-induced changes in adipose tissue, monocyte trafficking, and macro-/microvascular dysfunction are mediated by monocyte/macrophage dependent ROS generation of NAD(P)H oxidase pathway in p47phox-/- or gp91phox-/- mice that are deficient in critical component of NAD(P)H oxidase. Therefore, we intend to focus on white adipose tissue but systemically, mechanistically investigate the role of monocyte/macrophage in air pollution-induced adiposity and vascular dysfunction in both white and brown adipose tissues. By starting the exposure at age of 4 weeks in mice and exposure up to 24 weeks, we mimic the obesity development from childhood to adulthood in human. The findings from this proposal are expected to make significant contribution to better understanding the mechanisms of air pollution exposure on obesity development and associated vascular dysfunction, which may lead to the new policies/interventions in greener energy plants and automobiles, stricter air quality standards, and better, comprehensive obesity prevention.
Overweight and obesity cause significant public health burdens. This study will examine whether exposure to particulate air pollution causes increased inflammation in adipose tissues, induces adiposity in visceral fat tissue and vascular dysfunction, and decreases the metabolism in perivascular fat tissue.
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