Epidemiological studies have demonstrated that the general population’s exposure to bisphenol A (BPA) substitutes is ubiquitous. Bisphenol F (BPF), one of the main BPA substitutes, is increasingly replacing BPA in plastics for food and beverage applications. Accumulating evidence suggests that BPA exposure is associated with nonalcoholic fatty liver disease (NAFLD)-like changes. However, the potential effects of BPF on lipid homeostasis remain poorly understood. In the present study, an epidemiological analysis with LC-MS-MS revealed that the BPF concentrations in the serum of NAFLD patients were significantly higher than those in a control group. Supporting this result, using Oil Red O, BODIPY 493/503, LipidTox Deep Red staining and gas chromatography-time-of-flight mass spectrometry (TOF-MS) assays, we found that BPF exposure induced NAFLD-like changes, with obvious lipid droplet deposition, triglyceride (TG) and fatty acids increase in mouse livers. Meanwhile, lipid droplet deposition and TG increase induced by BPF were also observed in HepG2 cells, accompanied by autophagic flux blockade, including autophagosome accumulation and the decreased degradation of SQSTM1/p62. Using adenoviruses dual-reporter plasmid RFP-GFP-LC3, RFP-GFP-PLIN2 transfection, AO staining, and EGFR degradation assays, we demonstrated that BPF treatment impaired lysosomal degradative capacity, since BPF treatment obviously impaired lysosomal acidification, manifested as decreased lysosomal hydrolase cathepsin L (CTSL) and mature cathepsin D (CTSD) in HepG2 and mouse liver issues. Additionally, v-ATPase D, a multi-subunit enzyme that mediates acidification of eukaryotic intracellular organelles, significantly decreased after BPF exposure in both the vitro and in vivo studies.This study ascertained a novel mechanism involving dysfunctional of lysosomal degradative capacity induced by BPF, which contributes to lipophagic disorders and causes lipid droplet deposition. This work provides evidence that lysosomes may be a target organelle where BPF exerts its potential toxicity; therefore, novel intervention strategies targeting lysosome are promising for BPF-induced NAFLD-like changes.

Various microplastics (MPs) are found in the environment and organisms. MP residues in organisms can affect health; however, their impacts on metabolism in aquatic organisms remain unclear. In this study, zebrafish embryos were exposed to polyethylene MPs with sizes ranging from 1 to 4 μm at concentrations of 0, 10, 100, and 1000 μg/L for 7 days. Through qPCR technology, the results indicated that zebrafish exposed to polyethylene MPs exhibited significant change in microbes of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, etc. Moreover, 16S RNA gene sequencing revealed that there was a significant difference in alpha diversity between the control and 1000 μg/L MP-treated groups. At the genus level, the abundance of Aeromonas, Shewanella, Microbacterium, Nevskia and Methyloversatilis have increased remarkably. Conversely, the abundance of Pseudomonas, Ralstonia and Stenotrophomonas were significant reduction after MPs exposure. In addition, the levels of TG (triglyceride), TCHO (total cholesterol), NEFA (nonesterified fatty acid), TBA (total bile acid), GLU (glucose) and pyruvic acid significantly changed in MP-treated larval zebrafish, indicating that their metabolism was disturbed by MPs. Transcriptional levels of glucose and lipid metabolism-related genes showed a decreasing trend. Furthermore, LC/MS-based nontargeted metabolomics analysis demonstrated that a total of 59 phospholipid-related substances exhibited significant changes in larval fish treated with 1000 μg/L MPs. The mRNA levels of phospholipid metabolism-related genes were also obviously changed. Pearson correlation analysis indicated that the abundance of Aeromonas, Shewanella and Chitinibacter bacteria showed a negative correlation with most phospholipids, while Nevskia, Parvibacter and Lysobacter showed a positive correlation with most phospholipids. Based on these results, it is suggested that 1–4 μm PE-MPs could impact the microbiome and metabolism of larval zebrafish. All of these results indicated that the health risk of MPs cannot be ignored.

Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5 mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.

The effect of chronic exposure of freshwater cladoceran Daphnia magna to low, environmentally relevant concentrations i.e 4 μgL⁻¹of ibuprofen (a nonsteroidal anti-inflammatory drug) in a laboratory experiment was studied. We observed the key life history traits of first and fifth generation individuals: age and size at first reproduction, number of first clutch eggs and individual growth rate. Moreover, chosen molecular/subcellular markers of experimental animals stress response such as triglyceride content, heat shock proteins (HSP) expression and DNA:RNA ratio were collected. Overall, chronic exposure to ibuprofen had no significant effect on the molecular markers nor on the life history parameters of the Daphnia. It did, however, caused lethal morphological deformities in embryos and juvenile daphnids. Depending on the clonal affiliation, exposure to a low dosage of ibuprofen over five generations resulted in the deformation of ∼3%–∼10% of the first clutch of offspring. Also, up to 90% of females carried at least one deformed embryo. This is the first time that research has revealed such an effect of ibuprofen on D. magna.

Organophosphate esters (OPEs) are high-production volume chemicals. Use of OPEs has largely increased since the phase-out/ban of polybrominated diphenyl ethers (PBDEs). The ubiquitous occurrence of OPEs, in higher concentrations in abiotic matrices than brominated flame retardants (BFRs), is a concern because several of the OPEs have been linked to adverse health effects. In this study, urinary metabolites of OPEs were measured in a subset of a population-based sample of women of child bearing age recruited in Ontario, and associations between serum lipid levels and urinary concentrations of OPE metabolites were evaluated. Urine samples (n = 120) were extracted using automated solid phase extraction and analysed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Diphenyl phosphate (DPHP), bis(2-chloropropyl) phosphate (BCIPP) and bis(1,3-dichloro-2 propyl) phosphate (BDCIPP) were detected with frequencies of 100%, 76% and 75% at median concentrations of 13.8 ng/mL, 0.5 ng/mL and 1.8 ng/mL, respectively. Bis(2-chloroethyl) hydrogen phosphate (BCEP) and di-cresyl phosphate (DCP; mixture of 3 isomers) were detected in 52% and 42% of the samples, respectively. Detected at lower frequencies were 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 29%), bis-2(butoxyethyl) phosphate (BBOEP, 11%), and desbutyl-tris-(2-butoxy-ethyl) phosphate (desbutyl TBOEP, 9%). Using multiple regression model, a negative statistically significant correlation was observed between BCEP and cholesterol (p = 0.04), as well as BCEP and total lipid (p = 0.04). Whereas BCIPP was positively and significantly correlated with cholesterol (p = 0.003) and LDL (p = 0.001). Additional work to further explore these relationships and to evaluate more recently identified OPE metabolites is warranted.

N-nitrosamines (NAs) are an emerging group of disinfection by-products that occur as a mixture in drinking water. Although the potency of the individual NA components in drinking water is negligible, their combined effect is rarely reported. We tested whether multicomponent NAs mixtures at environmentally relevant levels would produce significant effects when each component was combined at extremely low concentrations i.e. a million times lower than its No Observed Effect Concentration (NOEC). Mixture L (the maximum values detected in drinking water) or mixture M (one order of magnitude higher than detected) were fed to male and female Sprague-Dawley (SD) rats since PND 28 for seven days. We found that the body weight gains and the triglyceride (TG) levels increased significantly in mixture M treated male rats. Correspondingly, an obesogenic microbiota profile was obtained in the mixture M treated young male rat: Firmicutes/Bacteroidetes and the obesity-related taxa including Alistipes, Ruminococcus were enriched. Collectively, this is the first in vivo demonstration of NAs mixtures at environmentally relevant levels. Despite the complicated relationship between gut microbiota and obesity, our study has demonstrated that changes in gut microbiota may contribute to the development of obesity after the exposure. Our results highlight that changes in gut microbiota could be a risk factor for obesity, which emphasizes the need to include gut microbiota in the traditional mammalian risk assessment.

Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARα, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes.

Despite the efforts of the European Commission to implement measures that offset the detrimental effects of agricultural intensification, farmland bird populations continue to decline. Pesticide use has been pointed out as a major cause of decline, with growing concern about those agro-chemicals that act as endocrine disruptors. We report here on the effects of flutriafol, a ubiquitous systemic fungicide used for cereal seed treatment, on the physiology and reproduction of a declining gamebird. Captive red-legged partridges (Alectoris rufa; n = 11–13 pairs per treatment) were fed wheat treated with 0%, 20% or 100% of the flutriafol application rate during 25 days in late winter. We studied treatment effects on the reproductive performance, carotenoid-based coloration and cellular immune responsiveness of adult partridges, and their relationship with changes in oxidative stress biomarkers and plasma biochemistry. We also studied the effect of parental exposure on egg antioxidant content and on the survival, growth and cellular immune response of offspring. Exposed partridges experienced physiological effects (reduced levels of cholesterol and triglycerides), phenotypical effects (a reduction in the carotenoid-based pigmentation of their eye rings), and most importantly, severe adverse effects on reproduction: a reduced clutch size and fertile egg ratio, and an overall offspring production reduced by more than 50%. No effects on body condition or cellular immune response of either exposed adult or their surviving offspring were observed. These results, together with previous data on field exposure in wild partridges, demonstrate that seed treatment with flutriafol represents a risk for granivorous birds; they also highlight a need to improve the current regulation system used for foreseeing and preventing negative impacts of Plant Protection Products on wildlife.

Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.

Cardiovascular toxicity of lead (Pb) manifests primarily as an effect on blood pressure and eventual increased risk of atherosclerosis and cardiovascular events. Therefore, we investigated vascular inflammatory biomarkers and cardiovascular effects of Pb-exposed children. A total of 590 children (3–7 years old) were recruited from Guiyu (n = 337), an electronic waste (e-waste)-exposed group, and Haojiang (n = 253), a reference group, from November to December 2016. We measured child blood Pb levels (BPbs), and systolic and diastolic blood pressure. Pulse pressure was calculated for the latter two. Serum biomarkers including lipid profiles and inflammatory cytokines, and plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) were detected. Unadjusted regression analysis illustrated that higher ln-transformed BPb associated with lower systolic blood pressure and pulse pressure. After adjustment for various confounders, the relational degree of lnBPb and blood pressure measures became slightly attenuated or not significant. Elevated BPb was associated with higher Lp-PLA2, interleukin (IL)-6, triglycerides (TG) and lower high-density lipoprotein (HDL). Lp-PLA2 remained inversely associated with pulse pressure and HDL, but positively with ratios of total cholesterol to HDL (Tc/HDL) and low-density lipoprotein to HDL (LDL/HDL). IL-6 was associated negatively with systolic blood pressure, pulse pressure and HDL, and positively associated with TG, Tc/HDL and LDL/HDL. The mediation effect of biomarkers on the association of BPb with pulse pressure was insignificant except for Lp-PLA2. Available data supports the conclusion that e-waste-exposed children with higher BPbs and concomitant abnormal measures of cardiovascular physiology have an augmented prevalence of vascular inflammation, as well as lipid disorder.