Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissues. Adipose tissue macrophages play critical roles in the establishment of the chronic inflammatory state and metabolic dysfunctions. The novel discovery that pro-inflammatory macrophages are recruited to obese adipose tissue prompted an increased interest in the interplay between immune cells and metabolism. Since this discovery, many works have been published investigating the factors that lead to macrophage recruitment, the phenotypic change of adipose tissue macrophages, and metabolic dysfunctions. Adipokines and chemokines are key mediators that play crucial roles in crosstalk between adipocytes and macrophages and in regulating the adipose tissue inflammation. In the present review, we discuss the obesity-mediated adipose tissue remodeling, and particularly, the role of adipokines/chemokines in macrophage recruitment to obese adipose tissue. This review provides new insights into the physiological role of these factors and identifies a potential therapeutic target for obesity and associated disorders.

Background: Exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown.Objectives: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation.Methods: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system.Results: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting α2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure–induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro-inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor–kappaB (NF-κB) pathway activation.Conclusion: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation.Citation: Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. 2014. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation. Environ Health Perspect 122:79–86; http://dx.doi.org/10.1289/ehp.1307151

Background: Epidemiologic and experimental studies support an association between PM2.5 exposure and insulin resistance (IR). Innate immune cell activation has been suggested to play a role in the pathogenesis of these effects.Objectives: We sought to evaluate the role of CC-chemokine receptor 2 (CCR2) in PM2.5-mediated inflammation and IR.Methods: Wild-type C57BL/6 and CCR2–/– male mice were fed a high-fat diet and exposed to either concentrated ambient PM2.5 or filtered air for 17 weeks via a whole-body exposure system. We evaluated glucose tolerance and insulin sensitivity. At euthanasia, blood, spleen, and visceral adipose tissue (VAT) were collected, and inflammatory cells were measured using flow cytometry. We used standard immunoblots, immunohistochemical methods, and quantitative PCR (polymerase chain reaction) to assess pathways of interest involving insulin signaling, inflammation, and lipid and glucose metabolism in various organs. Vascular function was assessed using myography.Results: PM2.5 exposure resulted in whole-body IR and increased hepatic lipid accumulation in the liver, which was attenuated in CCR2–/– mice by inhibiting SREBP1c-mediated transcriptional programming, decreasing fatty acid uptake, and suppressing p38 MAPK activity. Abnormal phosphorylation levels of AKT, AMPK in VAT, and adipose tissue macrophage content in wild-type mice were not present in CCR2–/– mice. However, the impaired whole-body glucose tolerance and reduced GLUT-4 in skeletal muscle in response to PM2.5 was not corrected by CCR2 deficiency.Conclusions: PM2.5 mediates IR by regulating VAT inflammation, hepatic lipid metabolism, and glucose utilization in skeletal muscle via both CCR2-dependent and -independent pathways. These findings provide new mechanistic links between air pollution and metabolic abnormalities underlying IR.Citation: Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. 2014. Air pollution–mediated susceptibility to inflammation and insulin resistance: influence of CCR2 pathways in mice. Environ Health Perspect 122:17–26; http://dx.doi.org/10.1289/ehp.1306841

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Extending social learning theory to a multi-level perspective, this study proposes a theoretical model that investigates both individual and team-level mechanisms that mediate the effect of ethical leadership on employee voice. Specifically, in terms of an individual-level social learning perspective, we suggest that an ethical leader acts as a prototype of a moral person (i.e. an ethical role model). From a team-level social learning perspective, we propose that, as a moral manager, team ethical leadership will foster an ethical climate within the team which will create a moral context that impacts employees' behaviors. In both instances, employee voice behaviors will be enhanced through these mechanisms. Evidencing the importance of the interaction between leader behaviors and context for leader effectiveness, we also show that employees are more likely to regard their ethical leaders as ethical role models in a team that highly values ethical conduct (i.e. high in ethical climate). Results obtained from 47 managers and 211 subordinates in China support our theoretical model. The theoretical and practical implications of our findings are also discussed.

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BackgroundPrior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development.MethodsKKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4–8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKβ inhibitor (IMD-0354) or TNFα antibody (infliximab) for 4–5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest.ResultsPM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Targeting the NFκB pathway with intra-cerebroventricular administration of an IKKβ inhibitor [IMD-0354, n = 8 for each group)], but not TNFα blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5.ConclusionsCentral inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM.