Inactivation of TNF/LT locus alters mouse metabolic response to concentrated ambient PM2.5
2017
Hu, Ziying | Chen, Minjie | Zhou, Huifen | Tharakan, Anui | Wang, Xiaoke | Qiu, Lianglin | Liang, Shuai | Qin, Xiaobo | Zhang, Yuhao | Wang, Wanjun | Xu, Yanyi | Ying, Zhekang
Exposure to ambient fine particulate matter (PM2.5) is associated with increased cardiometabolic morbidity and mortality. This is widely believed to be attributable to PM2.5 exposure-induced pulmonary and subsequent systemic inflammation. Tumor necrosis factor alpha (TNFα), lymphotoxin α (LTα), and lymphotoxin β (LTβ) are three homologous pro-inflammatory cytokines, each with both unique and redundant activities in inflammation. Their role in PM2.5 exposure-induced inflammation and adverse cardiometabolic effects has to be determined.LTα/TNFα/LTβ triple-knockout (TNF/LT KO) and wildtype (WT) mice were exposed to concentrated ambient PM2.5 (CAP) for 5 months. Lung pathological analysis revealed that TNF/LT deficiency reduced CAP exposure-induced pulmonary inflammation. However, glucose homeostasis assessments showed that TNF/LT deficiency significantly aggravated CAP exposure-induced glucose intolerance and insulin resistance. Consistent with glucose homeostasis assessments, CAP exposure significantly increased the body weight and adiposity of TNF/LT KO but not WT mice. In contrast to its body weight effects, CAP exposure reduced food intake of WT but not TNF/LT KO mice. On the other hand, CAP exposure induced marked fat droplet accumulation in brown adipose tissues of WT mice and significantly decreased their uncoupling protein 1 (UCP1) expression, and these effects were markedly exacerbated in TNF/LT KO mice.The present study suggests that TNF/LT deficiency influences PM2.5 exposure-induced response of energy metabolism through alterations in both food intake and energy expenditure.
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