Journal
TOXICOLOGY
Volume 390, Issue -, Pages 100-108Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2017.09.009
Keywords
Ambient PM2.5; Tumor necrosis factor; Lymphotoxin; Obesity; Inflammation
Categories
Funding
- National Institutes of Health [R01ES024516]
- American Heart Association [13SDG17070131]
- Shanghai Pujiang Program [17PJ1401300]
- National Natural Science Foundation of China [81270342, 21407082, 81302452, 81500216]
Ask authors/readers for more resources
Background: 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 (TNF alpha), lymphotoxin alpha (LT alpha), and lymphotoxin beta (LT beta) 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. Methods and results: LT alpha/TNF alpha/LT beta 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. Conclusion: 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available