2016 Progress Report: Southern California Children's Environmental Health Center

EPA Grant Number: R835441
Center: Southern California Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: Southern California Children's Environmental Health Center
Investigators: McConnell, Rob Scot , Gilliland, Frank D. , Finch, Caleb E , Bouret, Sebastien G. , Hricko, Andrea M. , Sattler, Fred R , Nayak, Krishna S. , Sioutas, Constantinos , Allayee, Hooman , Johnston, Jill , Berhane, Kiros , Goran, Michael , Mittelman, Steven , Morgan, Todd
Current Investigators: McConnell, Rob Scot
Institution: University of Southern California
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: July 1, 2013 through June 30, 2018 (Extended to June 30, 2019)
Project Period Covered by this Report: July 1, 2015 through June 30,2016
Project Amount: $4,146,875
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

Project 1: Effects of Air Pollution on the Development of Obesity in Children

Aim 1 will investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on body mass index (BMI) trajectory and obesity in the CHS cohort. We hypothesize that elevated exposure traffic-related air pollutant during the in utero and childhood periods are obesogenic and result in a steeper gender-specific trajectory of BMI increase with age and that cumulative exposures increase the prevalence of obesity at ages 5, 10 and 16 years.

Aim 2 will examine the effects of lifetime traffic-related air pollutant exposures on the visceral adipose tissue (VAT,) high fat fasting (HFF), superficial adipose tissue (SAT), deep SAT (dSAT) and superficial SAT (sSAT) in 200 overweight or obese 18-year-olds CHS participants sampled informatively based on EC2.5 exposure. We hypothesize that elevated exposure to EC2.5 will increase (1) the amount of VAT and dSAT relative to SAT, and (2) HFF and the prevalence of non-alcoholic fatty liver disease (NAFLD).
 
Aim 3 will investigate the effects of traffic-related air pollutant exposures on insulin sensitivity, pancreatic beta cell function, MetS and its components (blood pressure, glucose, lipid profile), adipokines and markers of inflammation (CRP, IL-6, TNF-α, MCP-1, leptin, resistin, adiponectin) in the 200 overweight or obese CHS 18-year-olds studied in Aim 2. We will assess VAT as a mediator for the chronic effects of exposure on adipokines, inflammatory markers, insulin sensitivity, pancreatic beta cell function and MetS using a novel quantile regression mediation approach. We hypothesize that after accounting for recent air pollution exposures (1) chronic traffic-related air pollutant exposures will increase metabolic dysfunction and the risk for MetS and (2) these adverse effects of chronic traffic exposures are mediated through VAT.

Project 2: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences

Aim 1: To investigate the effects of lifetime cumulative exposure to ambient near-roadway air pollution (NRAP) elemental carbon (EC) and NOx on macrophage polarization in deep SAT from M2 to pro-inflammatory M1 subtypes. We hypothesize that exposure to markers of the NRAP mixture [EC and oxides of nitrogen (NOx)] will be associated with increased proportion of M1/M2 macrophages and with the presence of clusters of nectoric macrophates [crown like structures (CLS)] in biopsy samples obtained from a novel deep subcutaneous adipost tissue (dSAT) biopsy.

Aim 2: To investigate the effects of lifetime exposure to NRAP on adipose tissue function and cell-specific gene expression. We hypothesize that high lifetime exposure to EC and NOx will be associated with (Aim 2a) increased expression of NFĸB inflammatory and insulin signaling pathway genes in macrophages and adipocyte subfractions of SAT, and (Aim 2b) greater release of adipocytokines and biochemical markers of insulin resistance from SAT biopsies incubated ex vivo.

Aim 3: To integrate information from P1 and P2 using a novel latent variable model to examine quantitatively the mechanisms underlying the entire pathway of NRAP effects on metabolic outcomes. The model will quantify the effects of exposure at different ages on a latent quantity such as underlying “adipose tissue inflammation.”

Project 3: Longitudinal Effects of Air Pollution on Obesity In Mice

Aim 1: We will determine the longitudinal effects of nanoscale particulate matter (nPM) exposure on the development of obesity and relevant physiological metabolic phenotypes. Mice in the control and exposed groups will undergo magnetic resonance imaging (MRI) to determine body composition (lean tissue mass and whole body fat) and fat distribution. We will also perform intraperitoneal glucose tolerance tests (IPGTTs) to assess glucose/insulin metabolism, measure a panel of adipocytokines in plasma, and determine hepatic lipid content.

Aim 2: We will characterize adipose tissue from mice for molecular, histological, and biochemical phenotypes. Immunohistochemistry will be used to determine the presence of crown-like structures (CLS) in adipose tissue, which is indicative of macrophage infiltration and inflammation. Adipocytes will be separated from the stromal vascular fraction, which will be used to perform flow cytometry to determine macrophage subtypes (M1/M2). The effects of nPM exposure on inflammatory and metabolic gene expression will be investigated in both isolated adipocytes and macrophages. Explant incubation studies will be carried out to determine in vitro production of adipocytokines. We hypothesize that nPM exposure will have progressively adverse effects on adipose tissue homeostasis, with increased inflammation at the cellular, secretory, and gene expression levels.
 
Aim 3: We will investigate whether the effects of nPM exposure on obesity are mediated through neurobiological pathways involved in metabolic regulation. Immunohistochemical techniques and morphometric analyses will be used to characterize the hypothalamus from nPM-exposed and control mice with respect to the organization of neural projections involved in feeding regulation. Expression of metabolically-relevant neuropeptide genes will also be investigated in a nucleus-specific manner by real-time PCR and food intake will be assessed to determine whether nPM exposure results in altered feeding behavior.
 

Community Outreach and Translation Core

Aim 1. Develop new constituencies and new media outlets for dissemination of research findings on near-roadway air pollution (NRAP) and its adverse health effects on children, including( a) advocates of physical activity to reduce obesity; and (b) advocates for new parks and outdoor exercise facilities and equitable access to green space in the city, including elected officials, urban planners, architects/landscape architects, land conservation and environmental justice (EJ) groups.
 
Aim 2. Build civic engagement in environmental health around the issues of air pollution and physical activity, by using youth-based participatory engagement techniques, working with youth from two communities with significant NRAP and high obesity rates.
 
Aim 3. Enhance the capacity of current community partners, new constituencies and youth to educate policymakers about the need to consider research findings on the adverse health effects of near-roadway air pollution, including obesity, when (a) siting new facilities to encourage physical activity, (b) expanding or building new highways or major roads close to where children play or exercise, and (c) considering new regulations to reduce air pollution to protect children’s health.
 
Aim 4. Evaluate the Community Outreach and Translation Core (COTC) efforts and share successful strategies and models with others at the local and national level; meet with community advisors and a formal community advisory committee.

Progress Summary:

All three projects have made substantial progress toward addressing Center goals. Recruitment of subjects is still ongoing for Projects 1 and 2. The first set of animal studies has been completed for P3 and results showing effects of air pollution on metabolic outcomes are summarized in a manuscript ready for submission. A followup experiment is underway to further characterize effects. The COTC has deepened working relationships with community counterparts and is actively engaged in providing the best information based on emerging science to outreach and translational activities. Additional details are provided in the individual project and core reports.

Project 1: Effects of Air Pollution on the Development of Obesity in Children

We have begun to investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. The exposure assessment has been completed from primary data including review of residential address histories, geocoding with state-of-the-art methods and updated land use regression models for exposure. For aims 2 and 3, we have assembled the study team, developed study materials and questionnaires, obtained IRB approvals, designed and programmed study databases, tested our data collection protocols, defined our exposure based sampling frame and completed 65 study participants for study visits. We had a slower start than anticipated but are now meeting our new recruiting target numbers after revising the protocol and increasing subject reimbursement. We anticipate meeting our targets in year 4 or 5.
 
Project 2: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences

We have refined procedures for collecting tissue and for assays. Cell sorting is done at the time of adipose tissue biopsy and we have successfully counted M1 and M2 macrophages. We have in addition counted Treg and Teff cells. Tissue for other assays is archived until data collection is completed. Results to date demonstrate broad distribution both of outcomes and lifetime exposure. Recruitment continues to be slower than anticipated in part because it is dependent on the recruitment from Project 1. Some issues with staff turnover have been resolved and a new recruitment mechanism better coordinated with P1 has been implemented. As Project 1 recruitment has increased, recruitment in Project 2 has also increased. More appropriate compensation for time and travel reimbursement also have increased recruitment. In addition, with advice from members of our external advisory committee, we have explored several additional approaches to recruitment, including targeting the study demographic and residence requirements in study zip codes through commercial listings obtained from InfoUSA and Scientific Telephone Survey, and we have settled on methods previously developed by Center Deputy Director and P2 co-investigator Michael Goran to recruit through advertising, targeting the communities where Children’s Health Study subjects live and restricting recruitment to lifetime southern California residents willing to have a fat biopsy. We anticipate this will maximize the exposure contrast (based on exposure-stratified sampling procedures developed in P1) in the appropriate age range, will provide complementary data to that we are continuing to recruit from the P1 pool, and will allow us sufficient sample size to complete all major goals. We will conduct sensitivity analyses using the participants recruited through P1. We anticipate we will be able to catch up and complete recruitment on the original time table within the next 12 months.

Project 3: Longitudinal Effects of Air Pollution on Obesity in Mice

During year 2 of the project, we first determined the effects of NRAP on obesity in mice that had whole life exposures. At the time of pregnancy, female C57BI/6J mice were exposed to either filtered air or 300µg/m3 nPM for 5 hours per day, 3 days per week. Subsequent to the birth of the pups, exposure was maintained in the same fashion until weaning at 4 weeks of age. Thereafter, male and female mice were put on either a regular chow diet (n = 8 males and n = 8 females) or a high fat diet (n = 8 males and n = 8 females) and exposure to filtered air or nPM was maintained in the same fashion for another 10 weeks. This study was completed at the beginning of year 3 in late March 2015. We carried out several non-invasive measurements including body weight and glucose metabolism. We observed that there were no differences in the body weights of female mice in any of the exposed or dietary groups. Therefore, we focused our efforts at the time of sacrifice on characterizing males with respect to adiposity, plasma metabolic biomarkers, and adipose gene expression.

As shown in Figure 1, male mice placed on the on the chow tended to gain more weight after exposure to nPM (panel A) but there were no differences in exposed and unexposed mice on the high fat (data not shown). The increase in body weight in chow-fed males was mostly attributable to increased fat mass but no effects on lean mass, which led to significantly increased adiposity (panel B). Placing the mice in metabolic cages further revealed that those exposed to nPM had increased food intake (FI), suggesting a behavioral component to the effects of exposure, but no differences in energy expenditure (EE) (Panel C). This was accompanied by nPM-exposed mice exhibiting impaired glucose clearance after being administered intraperitoneal glucose tolerance tests, with significantly higher area under the glucose tolerance curve (AUC) than control-exposed mice (Panel D). We next characterized adipose tissue with respect to gene expression and immune cell composition to determine whether changes in these phenotypes could explain the mechanism for the observed whole body physiological differences.

As shown in Figure 2, mRNA levels of insulin receptor (Insr) and insulin receptor substrates 1 and 2 (IRS1, IRS2) were all significantly decreased in adipose tissue of mice exposed to nPM. However, there were no differences in the expression of various adipocytokines (Panel A). Furthermore, there were no differences between the two groups of mice with respect to the number of effector T cells (Teffs), regulatory T cells (Tregs), and type 2 innate lymphoid cells (ILC2s) (Panel B), which have all been shown to modulate inflammation in adipose tissue and contribute to metabolic outcomes. In summary, mice fed a chow fat with exposure to nPM exhibit accumulation of adipose tissue, possibly through increased food intake, and decreased glucose clearance that is likely the result of increased insulin resistance at the level of adipose tissue. However, we do not believe these metabolic abnormalities are due to differences in the inflammatory profile of adipose. The results of these studies will also be of direct relevance to those collected in humans as part of Projects 1 and 2.

Community Outreach and Translation Core

In the 2015-2016 year, the COTC continued to partner with community organizations throughout the greater Los Angeles area. These targeted areas have high pollution burdens and health disparities, along with a lack of open space and parks. Working with the organizations and utilizing participatory engagement techniques, the COTC and youth groups selected tools for conducting environmental health audits of places where they play and exercise. These workshops and events have helped us work closely with organizations who work on environmental issues and obesity issues, in order to build their capacity to use the environmental health information. The strategies of community-based research projects and community tours has been successful in developing the leadership capacity of organization members, who then implement the information in their projects and campaigns.
 
Several organizations have partnered with the Outreach Core to investigate near-roadway traffic pollution in their neighborhoods through community air monitoring. Members chose hot spots of traffic in their neighborhoods, as well as comparison locations. They were trained on the equipment, then set out to monitor ultrafine particles and count traffic at several locations. This information is used in presentations to educate other residents about air pollution, as well as inform plans for projects to reduce air pollution and examine the needs for more green space.
 
At the Community-based Research Symposium in November 2015, more than 50 people attended to hear about several organizations’ projects related to air quality, traffic, and other health issues. A bus tour for community members in Long Beach, hosted by the COTC and five community partners, visited locations and discussed environmental health concerns at schools, the ports, freeways, refineries, and parks. Speakers at each stop discussed the community concerns, proposed projects, policies that are in place, health studies such as the USC children's health study, and the issue of air pollution as a barrier to exercise in many neighborhoods.
 
The “Green Spaces, Environmental Justice, and Public Health Roundtable” was a discussion organized by the Outreach Core and brought together over 50 stakeholders working on land use, urban planning, parks and recreation, public health and obesity. The event trained park advocates about the health concerns related to air pollution exposure and the emerging evidence linking such exposure to obesity. The discussion here developed key considerations for park siting in environmental justice communities, outlined best practices for involving local residents in the design of park facilities and fostering future collaborations between stakeholders working on parks, active transportation, air quality and physical activity.
 
In addition, the Outreach Core has taken leadership in address key issues of park and health inequities through the Los Angeles County Parks Needs Assessment. Through this collaboration with the County offices, community generated data on park quality and parks needs has been compiled. Core members have attended the planning meetings and engaging with new partners who are involved in this issue. One example is meeting with the Prevention Institute to gain background information and learn about ways to become involved. The Core staff then helped conduct outreach to additional partners to attend the park needs assessment meetings.
 

Future Activities:

Project 1: Effects of Air Pollution on the Development of Obesity in Children

We will continue to investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. The exposure assessment is now completed. Analyses are being conducted to understand the longitudinal effects of prenatal, early and later childhood exposure to traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. For aims 2 and 3, we will continue to assess study participants and conduct ongoing quality control and assurance activities.
 
Project 2: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences

The coming year will be focused on successfully completing recruitment.

Project 3: Longitudinal Effects of Air Pollution on Obesity In Mice

Our plans during the fourth year of Project 3 will be to carry out the two additional arms of the exposure studies. These are (1) exposing mice only during prenatal development and (2) exposing mice only during postnatal development. Based on our initial exposure study and feedback from the external advisory committee, we will focus mostly on the chow diet since nPM affected metabolic homeostasis in this setting. However, we will still consider a high fat-fed group of mice as well, possibly by using a diet that has lower fat content. In combination with the results from the already completed whole life exposure study, we expect to obtain additional insight into the critical windows of susceptibility during development that are important for exposure to NRAP. Overall, we do not anticipate any challenges to carrying out the studies in Project 3. Our pilot experiment has already yielded exciting results that are consistent with our hypothesis that NRAP promotes metabolic dysfunction.

Community Outreach and Translation Core

The COTC will continue to work with community partners and the Environmental Committee to host an Environmental Research Summer Institute in June and July, 2016. The partners planning the Institute include Asian and Pacific Islander Obesity Prevention Alliance, and Social Justice Learning Institute. This is a continuing series created to engage a diverse group of local high school youth from Lennox and South LA around environmental health and community research. The program is focused on educating, engaging, and empowering the youth to be agents of change in their own neighborhoods. Youth will learn about environmental health through workshops, presentations, and then placement with one of the community partner organizations to continue their project. The curriculum covered by the COTC includes gathering environmental data, community mapping, monitoring air and noise levels, and an introduction to the nonprofit and government agencies in the area.

The COTC will continue to respond to invitations to speak at community meetings and conferences, and technical assistance requests. We are actively developing relationships with urban planners at USC to engage in dialogue about the role in air pollution in land-use decision. Further, we are planning a commentary paper about the public health conflicts between outdoor physical activity and a polluted environment. The Core will also plan further events to be involved in the follow-up from the County Parks needs assessment and sharing research about potential risks from playing in parks affected by near roadway air pollution.


Journal Articles: 78 Displayed | Download in RIS Format

Other center views: All 82 publications 78 publications in selected types All 78 journal articles
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Journal Article Alderete TL, Autran C, Brekke BE, Knight R, Bode L, Goran MI, Fields DA. Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life. American Journal of Clinical Nutrition 2015;102(6):1381-1388. R835441 (2016)
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  • Journal Article Alderete TL, Habre R, Toledo-Corral CM, Berhane K, Chen Z, Lurmann FW, Weigensberg MJ, Goran MI, Gilliland FD. Longitudinal associations between ambient air pollution with insulin sensitivity, β-cell function, and adiposity in Los Angeles Latino children. Diabetes 2017;66(7):1789-1796. R835441 (2018)
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  • Journal Article Alderete TL, Jones RB, Chen Z, Kim JS, Habre R, Lurmann F, Gilliland FD, Goran MI. Exposure to traffic-related air pollution and the composition of the gut microbiota in overweight and obese adolescents. Environmental Research 2018;161:472-478. R835441 (2018)
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  • Journal Article Alderete TL, Song AY, Bastain T, Habre R, Toledo-Corral CM, Salam MT, Lurmann F, Gilliland FD, Breton CV. Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight. Pediatric Obesity 2018:13(6):348-356. R835441 (2018)
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  • Journal Article Allayee H, Hazen SL. Contribution of gut bacteria to lipid levels: another metabolic role for microbes? Circulation Research 2015;117(9):750-754. R835441 (2016)
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  • Journal Article Berger PK, Fields DA, Demerath EW, Fujiwara H, Goran MI. High-fructose corn-syrup-sweetened beverage intake increases 5-hour breast milk fructose concentrations in lactating women. Nutrients 2018;10(6):669 (9 pp.). R835441 (2018)
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  • Journal Article Bouret S, Levin BE, Ozanne SE. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiological Reviews 2015;95(1):47-82. R835441 (2016)
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  • Journal Article Breton CV, Mack WJ, Yao J, Berhane K, Amadeus M, Lurmann F, Gilliland F, McConnell R, Hodis HN, Kunzli N, Avol E. Prenatal air pollution exposure and early cardiovascular phenotypes in young adults. PLoS One 2016;11(3):e0150825 (12 pp.). R835441 (2016)
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  • Journal Article Chen Z, Salam MT, Toledo-Corral C, Watanabe RM, Xiang AH, Buchanan TA, Habre R, Bastain TM, Lurmann F, Wilson JP, Trigo E, Gilliland FD. Ambient air pollutants have adverse effects on insulin and glucose homeostasis in Mexican Americans. Diabetes Care 2016;39(4):547-554. R835441 (2016)
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  • Journal Article Chen Z, Salam MT, Alderete TL, Habre R, Bastain TM, Berhane K, Gilliland FD. Effects of childhood asthma on the development of obesity among school-aged children. American Journal of Respiratory and Critical Care Medicine 2017;195(9):1181-1188. R835441 (2018)
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  • Journal Article Cheng H, Davis DA, Hasheminassab S, Sioutas C, Morgan TE, Finch CE. Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro. Journal of Neuroinflammation 2016;13:19 (11 pp.). R835441 (2016)
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  • Journal Article Cho J, Goldenson NI, Pester MS, Khoddam R, Bello MS, Dunton GF, Belcher BR, Leventhal AM. Longitudinal associations between anhedonia and body mass index trajectory groups among adolescents. Journal of Adolescent Health 2018;63(1):81-87. R835441 (2018)
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  • Journal Article Cui X, Gong J, Han H, He L, Teng Y, Tetley T, Sinharay R, Chung KF, Islam T, Gilliland F, Grady S, Garshick E, Li Z, Zhang JJ. Relationship between free and total malondialdehyde, a well-established marker of oxidative stress, in various types of human biospecimens. Journal of Thoracic Disease 2018;10(5):3088-3097. R835441 (2018)
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  • Journal Article Dueker D, Taher M, Wilson J, McConnell R. Evaluating children's location using a personal GPS logging instrument: limitations and lessons learned. Journal of Exposure Science and Environmental Epidemiology 2014;24(3):244-252. R835441 (2015)
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  • Journal Article Dunton GF, O'Connor SG, Belcher BR, Maher JP, Schembre SM. Objectively-measured physical activity and sedentary time are differentially related to dietary fat and carbohydrate intake in children. Frontiers in Public Health 2018;6:198 (6 pp.). R835441 (2018)
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  • Journal Article Fruin S, Urman R, Lurmann F, McConnell R, Gauderman J, Rappaport E, Franklin M, Gilliland FD, Shafer M, Gorski P, Avol E. Spatial variation in particulate matter components over a large urban area. Atmospheric Environment 2014;83:211-219. R835441 (2015)
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  • Journal Article Ghazalpour A, Cespedes I, Bennett BJ, Allayee H. Expanding role of gut microbiota in lipid metabolism. Current Opinion in Lipidology 2016;27(2):141-147. R835441 (2016)
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  • Journal Article Ghosh R, Lurmann F, Perez L, Penfold B, Brandt S, Wilson J, Milet M, Kunzli N, McConnell R. Near-roadway air pollution and coronary heart disease: burden of disease and potential impact of a greenhouse gas reduction strategy in Southern California. Environmental Health Perspectives 2016;124(2):193-200. R835441 (2016)
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  • Journal Article Ghosh R, Gauderman WJ, Minor H, Youn HA, Lurmann F, Cromar KR, Chatzi L, Belcher B, Fielding CR, McConnell R. Air pollution, weight loss and metabolic benefits of bariatric surgery: a potential model for study of metabolic effects of environmental exposures. Pediatric Obesity 2018;13(5):312-320. R835441 (2017)
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  • Journal Article Goran MI, Martin AA, Alderete TL, Fujiwara H, Fields DA. Fructose in breast milk is positively associated with infant body composition at 6 months of age. Nutrients 2017;9(2)146 (11 pp.). R835441 (2018)
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  • Journal Article Habre R, Zhou H, Eckel SP, Enebish T, Fruin S, Bastain T, Rappaport E, Gilliland F. Short-term effects of airport-associated ultrafine particle exposure on lung function and inflammation in adults with asthma. Environment International 2018;118:48-59. R835441 (2018)
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  • Journal Article Hasson RE, Hsu YJ, Davis JN, Goran MI, Spruijt-Metz D. The influence of parental education on dietary intake in Latino youth. Journal of Immigrant and Minority Health 2018;20(1):250-254. R835441 (2018)
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  • Journal Article Hsieh S, Klassen AC, Curriero FC, Caulfield LE, Cheskin LJ, Davis JN, Goran MI, Weigensberg MJ, Spruijt-Metz D. Built environment associations with adiposity parameters among overweight and obese Hispanic youth. Preventive Medicine Reports 2015;2:406-412. R835441 (2016)
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  • Journal Article Hsieh S, Leaderer BP, Feldstein AE, Santoro N, McKay LA, Caprio S, McConnell R. Traffic-related air pollution associations with cytokeratin-18, a marker of hepatocellular apoptosis, in an overweight and obese paediatric population. Pediatric Obesity 2018;13(6):342-347. R835441 (2017)
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  • Journal Article Hsu TM, Konanur VR, Taing L, Usui R, Kayser BD, Goran MI, Kanoski SE. Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats. Hippocampus 2015;25(2):227-239. R835441 (2016)
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  • Journal Article Jerrett M, Shankardass K, Berhane K, Gauderman WJ, Künzli N, Avol E, Gilliland F, Lurmann F, Molitor JN, Molitor JT, Thomas DC, Peters J, McConnell R. Traffic-related air pollution and asthma onset in children: a prospective cohort study with individual exposure measurement. Environmental Health Perspectives 2008;116(10):1433-1438. R835441 (2017)
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  • Journal Article Jerrett M, McConnell R, Wolch J, Chang R, Lam C, Dunton G, Gilliland F, Lurmann F, Islam T, Berhane K. Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis. Environmental Health 2014;13:49 (9 pp.). R835441 (2015)
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  • Journal Article Kayser BD, Goran MI, Bouret SG. Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice. PLoS One 2015;10(3):e0121954 (15 pp.). R835441 (2016)
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  • Journal Article Kayser BD, Toledo-Corral CM, Alderete TL, Weigensberg MJ, Goran MI. Temporal relationships between adipocytokines and diabetes risk in Hispanic adolescents with obesity. Obesity 2015;23(7):1479-1485. R835441 (2016)
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  • Journal Article Kim JS, Alderete TL, Chen Z, Lurmann F, Rappaport E, Habre R, Berhane K, Gilliland FD. Longitudinal associations of in utero and early life near-roadway air pollution with trajectories of childhood body mass index. Environmental Health 2018;17(1):64 (10 pp.). R835441 (2018)
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  • Journal Article Kim JY, Goran MI, Toledo-Corral CM, Weigensberg MJ, Shaibi GQ. Comparing glycemic indicators of prediabetes: a prospective study of obese Latino Youth. Pediatric Diabetes 2015;16(8):640-643. R835441 (2016)
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  • Journal Article Li L, Lurmann F, Habre R, Urman R, Rappaport E, Ritz B, Chen JC, Gilliland FD, Wu J. Constrained mixed-effect models with ensemble learning for prediction of nitrogen oxides concentrations at high spatiotemporal resolution. Environmental Science & Technology 2017;51(17):9920-9929. R835441 (2018)
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  • Journal Article Lopez NV, Schembre S, Belcher BR, O'Connor S, Maher JP, Arbel R, Margolin G, Dunton GF. Parenting styles, food-related parenting practices, and children's healthy eating: a mediation analysis to examine relationships between parenting and child diet. Appetite 2018;128:205-213. R835441 (2018)
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  • Journal Article Luo S, O'Connor SG, Belcher BR, Page KA. Effects of physical activity and sedentary behavior on brain response to high-calorie food cues in young adults. Obesity 2018;26(3):540-546. R835441 (2018)
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  • Journal Article Lurmann F, Avol E, Gilliland F. Emissions reduction policies and recent trends in Southern California's ambient air quality. Journal of the Air & Waste Management Association 2015;65(3):324-335. R835441 (2016)
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  • Journal Article McConnell R, Shen E, Gilliland FD, Jerrett M, Wolch J, Chang C-C, Lurmann F, Berhane K. A longitudinal cohort study of body mass index and childhood exposure to secondhand tobacco smoke and air pollution: the Southern California Children's Health Study. Environmental Health Perspectives 2015;123(4):360-366. R835441 (2015)
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  • Journal Article McConnell R, Gilliland FD, Goran M, Allayee H, Hricko A, Mittelman S. Does near-roadway air pollution contribute to childhood obesity? Pediatric Obesity 2016;11(1):1-3. R835441 (2015)
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  • Journal Article Noble EE, Hsu TM, Jones RB, Fodor AA, Goran MI, Kanoski SE. Early-life sugar consumption affects the rat microbiome independently of obesity. The Journal of Nutrition 2017;147(1):20-28. R835441 (2018)
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  • Journal Article O'Connor SG, Ke W, Dzubur E, Schembre S, Dunton GF. Concordance and predictors of concordance of children's dietary intake as reported via ecological momentary assessment and 24 h recall. Public Health Nutrition 2018;21(6):1019-1027. R835441 (2018)
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  • Journal Article O'Reilly GA, Belcher BR, Davis JN, Martinez LT, Huh J, Antunez-Castillo L, Weigensberg M, Goran MI, Spruijt-Metz D. Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents. Obesity 2015;23(9):1886-1894. R835441 (2016)
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  • Journal Article Pomatto LCD, Cline M, Woodward N, Pakbin P, Sioutas C, Morgan TE, Finch CE, Forman HJ, Davies KJA. Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles ('vehicular smog'). Free Radical Biology and Medicine 2018;121:86-97. R835441 (2018)
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  • Journal Article Ritz B, Qiu J, Lee PC, Lurmann F, Penfold B, Erin Weiss R, McConnell R, Arora C, Hobel C, Wilhelm M. Prenatal air pollution exposure and ultrasound measures of fetal growth in Los Angeles, California. Environmental Research 2014;130:7-13. R835441 (2015)
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  • Journal Article Shankardass K, McConnell R, Jerrett M, Lam C, Wolch J, Milam J, Gilliland F, Berhane K. Parental stress increases body mass index trajectory in pre-adolescents. Pediatric Obesity 2014;9(6):435-442. R835441 (2015)
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  • Journal Article Smallwood T, Allayee H, Bennett BJ. Choline metabolites: gene by diet interactions. Current Opinion in Lipidology 2016;27(1):33-39. R835441 (2017)
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  • Journal Article Su JG, Jerrett M, McConnell R, Berhane K, Dunton G, Shankardass K, Reynolds K, Chang R, Wolch J. Factors influencing whether children walk to school. Health & Place 2013;22:153-161. R835441 (2015)
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  • Journal Article Tellez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcia A, Schnaas-Arrieta L, Wright RO, Hernandez-Avila M, Hu H. Longitudinal associations between blood lead concentrations lower than 10 μg/dL and neurobehavioral development in environmentally exposed children in Mexico City. Pediatrics 2006;118(2):e323-e330. R835441 (2017)
    R831725 (2007)
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  • Journal Article Toledo-Corral CM, Alderete TL, Richey J, Sequeira P, Goran MI, Weigensberg MJ. Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic versus normal glucose tolerant overweight and obese Latino adolescents. Acta Diabetologica 2015;52(2):277-284. R835441 (2016)
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  • Journal Article Toledo-Corral CM, Alderete TL, Habre R, Berhane K, Lurmann FW, Weigensberg MJ, Goran MI, Gilliland FD. Effects of air pollution exposure on glucose metabolism in Los Angeles minority children. Pediatric Obesity 2018;13(1):54-62. R835441 (2018)
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  • Journal Article Urman R, Gauderman J, Fruin S, Lurmann F, Liu F, Hosseini R, Franklin M, Avol E, Penfold B, Gilliland F, Brunekreef B, McConnell R. Determinants of the spatial distributions of elemental carbon and particulate matter in eight Southern Californian communities. Atmospheric Environment 2014;86:84-92. R835441 (2015)
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  • Journal Article Urman R, McConnell R, Islam T, Avol EL, Lurmann FW, Vora H, Linn WS, Rappaport EB, Gilliland FD, Gauderman WJ. Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants. Thorax 2014;69(6):540-547. R835441 (2015)
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  • Journal Article Vos MB, Goran MI. Sugar, sugar ... not so sweet for the liver.Gastroenterology 2017;153(3):642-645. R835441 (2018)
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  • Journal Article Wang P, Tuvblad C, Younan D, Franklin M, Lurmann F, Wu J, Baker LA, Chen JC. Socioeconomic disparities and sexual dimorphism in neurotoxic effects of ambient fine particles on youth IQ: a longitudinal analysis. PLoS One 2017;12(12):e0188731 (15 pp.). R835441 (2018)
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  • Journal Article Wheelock K, Zhang JJ, McConnell R, Tang D, Volk HE, Wang Y, Herbstman JB, Wang S, Phillips DH, Camann D, Gong J, Perera F. A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons. Environmental Science: Processes & Impacts 2018;20(5):780-789. R835441 (2018)
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  • Journal Article Wu W, Muller R, Berhane K, Fruin S, Liu F, Jaspers I, Diaz-Sanchez D, Peden DB, McConnell R. Inflammatory response of monocytes to ambient particles varies by highway proximity. American Journal of Respiratory Cell and Molecular Biology 2014;51(6):802-809. R835441 (2015)
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  • Journal Article Younan D, Tuvblad C, Li L, Wu J, Lurmann F, Franklin M, Berhane K, McConnell R, Wu AH, Baker LA, Chen JC. Environmental determinants of aggression in adolescents: role of urban neighborhood greenspace. Journal of the American Academy of Child and Adolescent Psychiatry 2016;55(7):591-601. R835441 (2018)
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  • Journal Article Younan D, Tuvblad C, Franklin M, Lurmann F, Li L, Wu J, Berhane K, Baker LA, Chen JC. Longitudinal analysis of particulate air pollutants and adolescent delinquent behavior in Southern California. Journal of Abnormal Child Psychology 2018;46(6):1283-1293. R835441 (2018)
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  • Journal Article Zigman JM, Bouret SG, Andrews ZB. Obesity impairs the action of the neuroendocrine ghrelin system. Trends in Endocrinology and Metabolism 2016;27(1):54-63. R835441 (2016)
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  • Journal Article Zink J, Belcher BR, Dzubur E, Ke W, O'Connor S, Huh J, Lopez N, Maher JP, Dunton GF. Association between self-reported and objective activity levels by demographic factors: ecological momentary assessment study in children. JMIR mHealth and uHealth 2018;6(6):e150 (12 pp.). R835441 (2018)
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  • Journal Article Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic related air pollution, particulate matter, and autism. JAMA Psychiatry 2013;70(1):71-77. R835441 (2017)
    R833292 (2012)
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  • Journal Article Alderete TL, Chen Z, Toledo-Corral CM, Contreras ZA, Kim JS, Habre R, Chatzi L, Bastain T, Breton CV, Gilliland FD. Ambient and traffic-related air pollution exposures as novel risk factors for metabolic dysfunction and type 2 diabetes. Current Epidemiology Reports 2018;5(2):79-91. R835441 (Final)
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  • Journal Article Liao Y, Schembre SM, O'Connor SG, Belcher BR, Maher JP, Dzubur E, Dunton GF. An electronic ecological momentary assessment study to examine the consumption of high-fat/high-sugar foods, fruits/vegetables, and affective states among women. Journal of Nutrition Education and Behavior 2018;50(6):626-631. R835441 (Final)
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  • Journal Article Vafeiadi M, Myridakis A, Roumeliotaki T, Chalkiadaki G, Dermitzaki E, Venihaki M, Sarri K, Vassilaki M, Leventakou V, Stephanou EG, Kogevinas M. Association of early life exposure to phthalates with obesity and cardiometabolic traits in childhood:sex specific associations. Frontiers in Public Health 2018;6:327. R835441 (Final)
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  • Journal Article Broadney MM, Belcher BR, Berrigan DA, Brychta RJ, Tigner IL, Shareef F, Papachristopoulou A, Hattenbach JD, Davis EK, Brady SM, Bernstein SB. Effects of interrupting sedentary behavior with short bouts of moderate physical activity on glucose tolerance in children with overweight and obesity:A randomized crossover trial. Diabetes care 2018;41(10):2220-2228. R835441 (Final)
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  • Journal Article Croteau‐Chonka DC, Chen Z, Barnes KC, Barraza‐Villarreal A, Celedón JC, Gauderman WJ, Gilliland FD, Krishnan JA, Liu AH, London SJ, Martinez FD. Gene coexpression networks in whole blood implicate multiple interrelated molecular pathways in obesity in people with asthma. Obesity 2018;26(12): 1938-1948. R835441 (Final)
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  • Journal Article Wen CK, Liao Y, Maher JP, Huh J, Belcher BR, Dzubur E, Dunton GF. Relationships among affective states, physical activity, and sedentary behavior in children:Moderation by perceived stress. Health Psychology 2018;37(10):904. R835441 (Final)
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  • Journal Article Casas M, Basagana X, Sakhi AK, Haug LS, Philippat C, Granum B, Manzano-Salgado CB, Brochot C, Zeman F, de Bont J, Andrusaityte S. Variability of urinary concentrations of non-persistent chemicals in pregnant women and school-aged children. Environment International 2018;121:561-573. R835441 (Final)
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  • Journal Article Voerman E, Santos S, Inskip H, Amiano P, Barros H, Charles MA, Chatzi L, Chrousos GP, Corpeleijn E, Crozier S, Doyon M. Association of gestational weight gain with adverse maternal and infant outcomes. Jama 2019;321(17):1702-1715. R835441 (Final)
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  • Journal Article Galle-Treger L, Sankaranarayanan I, Hurrell BP, Howard E, Lo R, Maazi H, Lewis G, Banie H, Epstein AL, Hu P, Rehan VK. Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes. Nature Communications 2019;10(1):713. R835441 (Final)
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  • Journal Article Belcher BR, Maher JP, Lopez NV, Margolin G, Leventhal AM, Ra CK, O’Connor S, Gruenewald TL, Huh J, Dunton GF. Dual versus single parental households and differences in maternal mental health and child’s overweight/obesity. Maternal and Child Health Journal 2019;23(4):547-556. R835441 (Final)
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  • Journal Article Woodward NC, Crow AL, Zhang Y, Epstein S, Hartiala J, Johnson R, Kocalis H, Saffari A, Sankaranarayanan I, Akbari O, Ramanathan G. Exposure to nanoscale particulate matter from gestation to adulthood impairs metabolic homeostasis in mice. Scientific Reports 2019;9(1):1816. R835441 (Final)
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  • Journal Article Nieuwenhuijsen MJ, Agier L, Basagaña X, Urquiza J, Tamayo-Uria I, Giorgis-Allemand L, Robinson O, Siroux V, Maitre L, de Castro M, Valentin A. Influence of the urban exposome on birth weight. Environmental Health Perspectives 2019;127(4):047007. R835441 (Final)
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  • Journal Article Warrington NM, Beaumont RN, Horikoshi M, Day FR, Helgeland O, Laurin C, Bacelis J, Peng S, Hao K, Feenstra B, Wood AR. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nature Genetics 2019;51(5):804-814. R835441 (Final)
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  • Journal Article Voerman E, Santos S, Golab BP, Amiano P, Ballester F, Barros H, Bergstrom A, Charles MA, Chatzi L, Chevrier C, Chrousos GP. Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood:an individual participant data meta-analysis. PLoS Medicine 2019;16(2):e1002744. R835441 (Final)
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  • Journal Article Alderete TL, Jin R, Walker DI, Valvi D, Chen Z, Jones DP, Peng C, Gilliland FD, Berhane K, Conti DV, Goran MI. Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children:a proof-of-concept analysis. Environment International 2019;126:445-453. R835441 (Final)
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  • Journal Article Lopez NV, Yang CH, Belcher BR, Margolin G, Dunton GF. Within-subject associations of maternal physical activity parenting practices on children’s objectively measured moderate-to-vigorous physical activity. Journal of Pediatric Psychology 2019;44(3):300-310. R835441 (Final)
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  • Journal Article O’Connor SG, Habre R, Bastain TM, Toledo-Corral CM, Gilliland FD, Eckel SP, Cabison J, Naya CH, Farzan SF, Chu D, Chavez TA. Within-subject effects of environmental and social stressors on pre-and post-partum obesity-related biobehavioral responses in low-income Hispanic women:protocol of an intensive longitudinal study. BMC Public Health 2019;19(1):253. R835441 (Final)
    R836158 (2019)
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  • Journal Article Jones RB, Alderete TL, Kim JS, Millstein J, Gilliland FD, Goran MI. High intake of dietary fructose in overweight/obese teenagers associated with depletion of Eubacterium and Streptococcus in gut microbiome. Gut Microbes 2019:1-8. R835441 (Final)
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  • Journal Article Chen Z, Herting MM, Chatzi L, Belcher BR, Alderete TL, McConnell R, Gilliland FD. Regional and traffic-related air pollutants are associated with higher consumption of fast food and trans fat among adolescents. The American Journal of Clinical Nutrition. 2018;109(1):99-108. R835441 (Final)
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  • Supplemental Keywords:

    Children's health, children's environmental health, near-roadway air pollution, NRAP, air pollution, adverse health effects, obesity, air pollutant

    Progress and Final Reports:

    Original Abstract
  • 2014 Progress Report
  • 2015 Progress Report
  • 2017 Progress Report
  • 2018 Progress Report
  • Final Report