Effects of exposure to ambient fine particulate matter on the heart of diet-induced obesity mouse model.

Exposure to fine particulate matter (PM 2.5) is associated with decreased cardiac function, especially in high risk populations such as obese ones. In this study, impacts of PM 2.5 exposure on cardiac function were investigated by using the diet-induced obesity mice model. Mice were fed with normal diet or high-fat diet (HFD) for four weeks and then exposed to phosphate-buffered solution or Taiyuan winter PM 2.5 (0.25 mg/kg body/day) through intratracheal instillation for another four weeks. Among physiological indices recorded, heart rate and blood pressure were increased after PM 2.5 exposure in the heart of the obese mice. Metabolomics and lipidomics were applied to explore molecular alterations in response to the co-treatment of PM 2.5 and HFD. Our results demonstrated both direct impacts on cardiac function and indirect effects resulted from the injury of other organs. Inflammation of lung and hypothalamus may be responsible for the elevation of phenylalanine metabolism in serum and its downstream products: epinephrine and norepinephrine, the catecholamines involves in regulating cardiac system. In intracardiac system, the co-treatment led to imbalance of energy metabolism, in addition to oxidative stress and inflammation. In contrast to the upregulation of glucose and fatty acids uptake and CoA synthesis, levels of ATP, acetyl-CoA and the intermediates in glycolysis pathway decreased in the heart. The results indicated that energy metabolism disorder was possibly one of the important contributing factors to the more severe adverse effects of the combined treatment of HFD and PM 2.5. Unlabelled Image • PM 2.5 increased heart weight, heart rate and blood pressure in obese mice. • PM 2.5 activated phenylalanine metabolism by hypothalamus inflammation in obese mice. • PM 2.5 disturbed energy metabolism and caused lipotoxicity in hearts of obese mice. • PM 2.5 induced more severe cardiotoxicity in obese mice than normal mice. [ABSTRACT FROM AUTHOR]