Role of formyl peptide receptor 2 in steatosis of L02 cells exposed to Mono-(2-ethylhexyl) phthalate.

Mono-(2-ethylhexyl) phthalate (MEHP) can accumulate in the liver and then lead to hepatic steatosis, while the underlying mechanism remains unclear. Inflammation plays an important role in the disorder of hepatic lipid metabolism. This study aims to clarify the role of the inflammatory response mediated by formyl peptide receptor 2 (FPR2) in steatosis of L02 cells exposed to MEHP. L02 cells were exposed to MEHP of different concentrations and different time. A steatosis model of L02 cells was induced with oleic acid and the cells were exposed to MEHP simultaneously. In addition, L02 cells were incubated with FPR2 antagonist and then exposed to MEHP. Lipid accumulation was determined by oil red O staining and extraction assay. The indicators related to lipid metabolism and inflammatory response were measured with appropriate kits. The relative expression levels of FPR2 and its ligand were determined by Western blot, and the interaction of them was detected by co-immunoprecipitation. As a result, MEHP exposure could promote the occurrence and progression of steatosis and the secretion of chemokines and inflammatory factors in L02 cells. MEHP could also affect the expression and activation of FPR2 and the secretion of FPR2 ligands. In addition, the promotion effect of MEHP on the secretion of total cholesterol and interleukin 1ß in L02 cells could be significantly inhibited by the FPR2 antagonist. We concluded that FPR2 might affect the promotion effect of MEHP on steatosis of L02 cells by mediating inflammatory response.

Effects of fuel and driving conditions on particle number emissions of China-VI gasoline vehicles: based on corrections to test results.

The increasing number of vehicles are emitting a large amount of particles into the atmosphere, causing serious harm to the ecological environment and human health. This study conducted the Worldwide Harmonized Light Vehicles Test Cycle (WLTC) to investigate the emission characteristics of particle number (PN) of China-VI gasoline vehicles with different gasoline. The gasoline with lower aromatic hydrocarbons and olefins reduced particulate matter (PM) and PN emissions by 24% and 52% respectively. The average PN emission rate of the four vehicles during the first 300 s (the cold start period) was 7.2 times that of the 300 s-1800s. Additionally, because the particle transmission time and instrument response time, the test results of instantaneous emissions of PN were not synchronized with vehicle specific power (VSP). By calculating the Spearman correlation coefficient between pre-average vehicle specific power (PAVSP) and the test results of PN instantaneous emissions, the delay time was determined as 10s. After the PN emissions results were corrected, the PN emissions were found to be more related to VSP. By analyzing the influence of driving status on emission, this study found that vehicles in acceleration mode increased PN emissions by 76% compared to those in constant speed mode.

Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP.

OBJECTIVE: MEHP, as the metabolite of DEHP, is a widely used environmental endocrine disruptor. Ovarian granulosa cells participate in maintaining the function of ovary and COX2/PGE2 pathway may regulate the function of granulosa cells. We aimed to explore how COX-2/PGE2 pathway affects cell apoptosis in ovarian granulosa cells caused by MEHP. METHODS: Primary rat ovarian granulosa cells were treated with MEHP (0, 200, 250, 300 and 350 µM) for 48 h. Adenovirus was used for over-expression of COX-2 gene. The cell viability was tested with CCK8 kits. The apoptosis level was tested by flow cytometry. The levels of PGE2 were tested with ELISA kits. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and apoptosis-related genes, were measured with RT-qPCR and Western blot. RESULTS: MEHP decreased the cell viability. After MEHP exposure, the cell apoptosis level increased. The level of PGE2 markedly decreased. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and anti-apoptotic genes decreased; the expression levels of pro-apoptotic genes increased. The apoptosis level was alleviated after over-expression of COX-2, and the level of PGE2 slightly increased. The expression levels of PTGER2 and PTGER4, and the levels of ovulation-related genes increased; the levels of pro-apoptotic genes decreased. CONCLUSION: MEHP can cause cell apoptosis by down-regulating the levels of ovulation-related genes via COX-2/PGE2 pathway in rat ovarian granulosa cells.

Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 µM) for 24 h. About 50 µM DAPT and 100 µg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1ß. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

PM2.5 induces the abnormal lipid metabolism and leads to atherosclerosis via Notch signaling pathway in rats.

PM2.5 can affect the lipid metabolism and cause atherosclerosis. Abnormal lipid metabolism is a sever risk factor of atherosclerosis and the underlying molecular mechanism still remains unclear. In this study, GPL16956 Agilent-045997 Arraystar human lncRNA microarray V3 (Probe Name Version) platform was used to detect the different genes of lipid metabolism between the normal arterial intima and advanced atherosclerotic plaque, which were downloaded from GEO database. A high-fat diet and vitamin D3 were administered to Wistar rats to establish the atherosclerotic model and another normal healthy 56 rats were used as the non-atherosclerotic exposure groups. The atherosclerotic rats and non-atherosclerotic rats were randomly divided into 4 PM2.5 groups (0, 1.5, 7.5, 37.5 mg/kg), respectively. The results of bioinformatics showed changes in the Notch1, Dll1, Hes1, LDLR and ABCG1 levels. PM2.5 exposure could produce damage to the physiological structure of the aorta, and aggravate atherosclerosis in rats from both non-atherosclerotic and atherosclerotic groups. With the increase of the exposure dose, the levels of TC and TG significantly increased. PM2.5 exposure significantly affected the expression levels of PPARγ, ABCA1, LDLR, CD36, SR-BI and SREBP2. PM2.5 exposure could also affect the expression levels of the Notch signaling pathways which was significantly correlated with the levels of TC and TG. The results proved that PM2.5 exposure could induce and aggravate the atherosclerosis in rats by disrupting lipid metabolism in which Notch signaling pathway may play a significant role.

Nanoplastics and Microplastics May Be Damaging Our Livers.

Plastics in the environment can be degraded and even broken into pieces under the action of natural factors, and the degraded products with a particle size of less than 5 mm are called microplastics (MPs). MPs exist in a variety of environmental media that come into contact with the human body. It can enter the body through environmental media and food chains. At present, there are many studies investigating the damage of MPs to marine organisms and mammals. The liver is the largest metabolizing organ and plays an important role in the metabolism of MPs in the body. However, there is no available systematic review on the toxic effects of MPs on the liver. This paper summarizes the adverse effects and mechanisms of MPs on the liver, by searching the literature and highlighting the studies that have been published to date, and provides a scenario for the liver toxicity caused by MPs.

Effect of Acute Cold Exposure on Energy Metabolism and Activity of Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis.

Background: The benefit of cold exposure for humans against obesity has brought the energy metabolism and activity of brown adipose tissue (BAT) induced by cold into focus. But the results are inconsistent. This review is aimed to systematically explore the effect of cold exposure on the activity of BAT and energy metabolism in humans. Methods: We searched relevant papers that were published from 1990 to 2021 and were cited in PubMed Central, Web of science, Embase and Cochrane Library databases to conduct this systematic review and meta-analysis. Energy metabolism, BAT volume, BAT activity and non-esterified fatty acids (NEFA) data reported in eligible researches were extracted. Meta-analysis was applied to combine the mean difference or standard mean difference with their 95% confidence intervals (95%CI). RevMan 5.3 software was used for meta-analysis and evaluating the risk of bias. Stata 16.0 was used for evaluating the publication bias. Results: Ten randomized controlled trials were included in meta-analysis. Compared with human exposed in room temperature at 24°C, the energy expenditure (EE) was increased after acute cold exposure at 16∼19°C (Z = 7.58, p < 0.05, mean different = 188.43kal/d, 95% CI = 139.73-237.13); BAT volume (Z = 2.62, p < 0.05; standard mean different = 0.41, 95% CI = 0.10-0.73); BAT activity (Z = 2.05, p = 0.04, standard mean difference = 1.61, 95% CI = 0.07-3.14) and the intake of BAT NEFA (Z = 2.85, p < 0.05; standard mean different = 0.53, 95% CI = 0.17-0.90) also increased. Conclusion: Acute cold exposure could improve the energy expenditure and BAT activity in adults, which is beneficial for human against obesity.