Type 2 diabetes mellitus (T2DM) is one of the leading causes of death around the world. Epidemiological studies have uncovered that in addition to lack of exercise and over-nutrition, factors in the physical environment such as pollutants may also be associated with T2DM. We and others have provided evidence that airborne particulate matter <2.5 ?m (PM2.5) exposure modulates key processes in the pathogenesis of T2DM including insulin resistance, visceral fat accumulation, pro-inflammatory immune activation, and hepatic endoplasmic reticulum stress. Integrated pathways by which exposure may modulate these diverse effects are currently lacking. In this proposal, we postulate that PM2.5 exposure induces hypothalamic Inhibitor ?B Kinase 2 (IKK2)/Nuclear Factor-?B (NF-?B) activation with consequent changes in peripheral insulin sensitivity/inflammation, and thus propose to pursue 3 discrete yet linked aims using state of art in vivo exposures that mimic real-world exposure to air pollution.
Aim 1 : To determine if PM2.5 exposure induces hypothalamic IKK2/NF-?B activation and inflammatory response.
Aim 2 : To determine if central IKK2/NF-?B signaling is essential for PM2.5 exposure-induced abnormalities in insulin sensitivity/inflammation.
Aim 3. To determine if TNF? is essential for PM2.5 exposure-induced hypothalamic inflammation and insulin resistance. Our results will provide a renewed understanding of the protean effects of air pollution exposure and have obvious global public health implications.

Public Health Relevance

Airborne particles, the main ingredient of haze, smoke, and airborne dust, present serious air quality problems in many areas of the United States, and can occur year-round and cause a number of serious health problems, even at concentrations found in many major cities. This project investigates the role of central nervous system in airborne particle exposure-induced diabetes. The results will not only provide insight into the mechanism whereby airborne particle exposure leads to diabetes but also facilitate the development of new models and preventions for this serious public health risk.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-DKUS-C (90))
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Heindel, Jerrold
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University of Maryland Baltimore
Internal Medicine/Medicine
Schools of Medicine
United States
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Au, Dianaly T; Ying, Zhekang; Hernández-Ochoa, Erick O et al. (2018) LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Regulates Smooth Muscle Contractility by Modulating Ca2+ Signaling and Expression of Cytoskeleton-Related Proteins. Arterioscler Thromb Vasc Biol 38:2651-2664
Chen, Sufang; Wei, Wei; Chen, Minjie et al. (2018) TNF Signaling Impacts Glucagon-Like Peptide-1 Expression and Secretion. J Mol Endocrinol 61:153-161
Qiu, Lianglin; Chen, Minjie; Wang, Xiaoke et al. (2018) Exposure to Concentrated Ambient PM2.5 Compromises Spermatogenesis in a Mouse Model: Role of Suppression of Hypothalamus-Pituitary-Gonads Axis. Toxicol Sci 162:318-326
Chen, Minjie; Liang, Shuai; Qin, Xiaobo et al. (2018) Prenatal exposure to diesel exhaust PM2.5 causes offspring ? cell dysfunction in adulthood. Am J Physiol Endocrinol Metab 315:E72-E80
Wang, Wanjun; Zhou, Ji; Chen, Minjie et al. (2018) Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model. Part Fibre Toxicol 15:17
Chen, Minjie; Qin, Xiaobo; Qiu, Lianglin et al. (2018) Concentrated Ambient PM2.5-Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency. Environ Health Perspect 126:027003
Chen, Minjie; Liang, Shuai; Zhou, Huifen et al. (2017) Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism. Part Fibre Toxicol 14:3
Wang, Xiaoke; Chen, Minjie; Zhong, Mianhua et al. (2017) Exposure to Concentrated Ambient PM2.5 Shortens Lifespan and Induces Inflammation-Associated Signaling and Oxidative Stress in Drosophila. Toxicol Sci 156:199-207
Hu, Ziying; Chen, Minjie; Zhou, Huifen et al. (2017) Inactivation of TNF/LT locus alters mouse metabolic response to concentrated ambient PM2.5. Toxicology 390:100-108
Chen, Minjie; Wang, Xiaoke; Hu, Ziying et al. (2017) Programming of mouse obesity by maternal exposure to concentrated ambient fine particles. Part Fibre Toxicol 14:20

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