Rising evidence of both experimental and epidemiological studies suggests that phthalate exposure may contribute to increased risks of metabolic disorders. But there is limited research on the childhood dyslipidemia. Our cohort study was conducted in Xiamen city, Fujian Province, China. A total of 829 children (mean age 8.5 years) were included with collection of urine, blood samples and demographic data in May 2018 and followed up once a year from 2018 to 2020. We performed adjusted log-binomial regressions to examine associations between sex-specific tertiles of seven phthalate metabolites and dyslipidemia in visit 1, as well as persistent dyslipidemia and occasional dyslipidemia. We also used generalized estimating equation models (GEE) to explore the relationships between log-transformed phthalate metabolites and lipid profiles. In adjusted models, the prevalence and RRs of dyslipidemia increased with tertile group of mono-n-butyl phthalate (MnBP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), and summed di-(2-ethylhexyl) phthalate (∑DEHP) metabolites with a dose-response relationship in visit 1, as well as persistent dyslipidemia. Higher MnBP, ∑LMWP, MEHHP, MEOHP, and ∑DEHP concentrations were also associated with higher levels of log-transformed triglycerides (TG). Boys were more vulnerable to phthalates exposure than girls. In conclusion, children in China were widely exposed to phthalates, and phthalates exposure during childhood might significantly increase the risk of dyslipidemia and a higher level of lipid profiles, particularly in boys.

Phenanthrene (Phe) is a polycyclic aromatic hydrocarbon widely present in foods and drinking water. To explore the detrimental effects of Phe on body metabolism, female Kunming mice were treated with Phe in drinking water at concentrations of 0.05, 0.5 and 5 ng/mL. After exposure for 270 d, the animals exhibited dose-dependent reduced body weight and increased water consumption. The dose-dependent accumulation of Phe in the brain decreased hypothalamic neuron numbers, upregulated hypothalamic expression of anaplastic lymphoma kinase, elevated norepinephrine levels in white adipose tissue (WAT) and further activated lipolysis in WAT, leading to a reduction in fat mass. Brown adipose tissue formation was reduced, accompanied by the inhibition of the bone morphogenetic protein signaling pathway. A simultaneous reduced serum levels of antidiuretic hormone (arginine vasopressin) might be one of the reasons for increased water consumption. The present results indicate an environmental etiology and prevention way for the development of emaciation-thirst disease.

Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.

Ambient particles with aerodynamic diameter <0.1 μm (PM₀.₁) have been suggested to have significant health impact. However, studies on the association between long-term PM₀.₁ exposure and human blood lipid metabolism are still limited. This study was aimed to evaluate such association based on multiple lipid biomarkers and dyslipidemia indicators. We matched the 2006–2009 average PM₀.₁ concentration simulated using the neural-network model following the WRF-Chem model with the clinical and questionnaire data of 15,477 adults randomly recruited from 33 communities in Northeast China in 2009. After controlling for social demographic and behavior confounders, we assessed the association of PM₀.₁ concentration with multiple lipid biomarkers and dyslipidemia indicators using generalized linear mixed-effect models. Effect modification by various social demographic and behavior factors was examined. We found that each interquartile range increase in PM₀.₁ concentration was associated with a 5.75 (95% Confidence interval, 3.24–8.25) mg/dl and a 6.05 (2.85–9.25) mg/dl increase in the serum level of total cholesterol and LDL-C, respectively. This increment was also associated with an odds ratio of 1.25 (1.10–1.42) for overall dyslipidemias, 1.41 (1.16, 1.73) for hypercholesterolemia, and 1.90 (1.39, 2.61) for hyperbetalipoproteinemia. Additionally, we found generally greater effect estimates among the younger participants and those with lower income or with certain behaviors such as high-fat diet. The deleterious effect of long-term PM₀.₁ exposure on lipid metabolism may make it an important toxic chemical to be targeted by future preventive strategies.

There is a scarcity of studies on the interactions between heavy metals and non-alcoholic fatty liver disease (NAFLD). Using a variety of statistical approaches, we investigated the impact of three common heavy metals on liver enzymes and NAFLD markers in a Korean adult population. We observed that cadmium, mercury, and lead all demonstrated positive correlations with liver enzymes and NAFLD indices. Our findings were mostly robust in secondary analysis, which included three novel mixture modeling approaches (WQS, qgcomp, and BKMR) as well as in silico investigation of molecular mechanisms (genes, miRNAs, biological processes, pathways, and illnesses). The 16 genes interacted with a mixture of heavy metals, which was linked to the development of NAFLD. Co-expression was discovered in nearly half of the interactions between the 18 NAFLD-linked genes. Key molecular pathways implicated in the pathogenesis of NAFLD generated by the heavy metal combination include activated oxidative stress, altered lipid metabolism, and increased cytokines and inflammatory response. Heavy metal exposure levels were related to liver enzymes and NAFLD indices, and cutoff criteria were revealed. More studies are needed to validate our findings and gain knowledge about the effects of chronic combined heavy metal exposure on adult and child liver function and the likelihood of developing NAFLD. To reduce the occurrence of NAFLD, early preventative and regulatory actions (half-yearly screening of workers at high-risk facilities; water filtration; avoiding excessive amounts of seafood, etc.) should be taken.

With the widespread occurrence and accumulation of plastic waste in the world, plastic pollution has become a serious threat to ecosystem and ecological security, especially to estuarine and coastal areas. Understanding the impacts of changing nanoplastics concentrations on aquatic organisms living in these areas is essential for revealing the ecological effects caused by plastic pollution. In the present study, we revealed the effects of exposure to gradient concentrations (0.005, 0.05, 0.5 and 50 mg/L) of 75 nm polystyrene nanoplastics (PS-NPs) for 48 h on metabolic processes in muscle tissue of a bivalve, the razor clam Sinonovacula constricta, via metabolomic and transcriptomic analysis. Our results showed that PS-NPs caused dose-dependent adverse effects on energy reserves, membrane lipid metabolism, purine metabolism and lysosomal hydrolases. Exposure to PS-NPs reduced energy reserves, especially lipids. Membrane lipid metabolism was sensitive to PS-NPs with contents of phosphocholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS) increasing and degradation being inhibited in all concentrations. High concentrations of PS-NPs altered the purine metabolism via increasing contents of guanosine triphosphate (GTP) and adenine, which may be needed for DNA repair, and consuming inosine and hypoxanthine. During exposure to low concentrations of PS-NPs, lysosomal hydrolases in S. constricta, especially cathepsins, were inhibited while this influence was improved transitorily in 5 mg/L of PS-NPs. These adverse effects together impacted energy metabolism in S. constricta and disturbed energy homeostasis, which was manifested by the low levels of acetyl-CoA in high concentrations of PS-NPs. Overall, our results revealed the effects of acute exposure to gradient concentrations of PS-NPs on S. constricta, especially its metabolic process, and provide perspectives for understanding the toxicity of dynamic plastic pollution to coastal organisms and ecosystem.

Silver nanomaterials (AgNMs) are broadly used and among the most studied nanomaterials. The underlying molecular mechanisms (e.g. protein and metabolite response) that precede phenotypical effects have been assessed to a much lesser extent. In this paper, we assess differentially expressed proteins (DEPs) and metabolites (DEMs) by high-throughput (HTP) techniques (HPLC-MS/MS with tandem mass tags, reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) with mass spectrometric detection). In a time series (0, 7, 14 days), the standard soil model Enchytraeus crypticus was exposed to AgNM300K and AgNO₃ at the reproduction EC20 and EC50. The impact on proteins/metabolites was clearly larger after 14 days. NM300K caused more upregulated DEPs/DEMs, more so at the EC20, whereas AgNO₃ caused a dose response increase of DEPs/DEMs. Similar pathways were activated, although often via opposite regulation (up vs down) of DEPs, hence, dissimilar mechanisms underlie the apical observed impact. Affected pathways included e.g. energy and lipid metabolism and oxidative stress. Uniquely affected by AgNO₃ was catalase, malate dehydrogenase and ATP-citrate synthase, and heat shock proteins (HSP70) and ferritin were affected by AgNM300K. The gene expression-based data in Adverse Outcome Pathway was confirmed and additional key events added, e.g. regulation of catalase and heat shock proteins were confirmed to be included. Finally, we observed (as we have seen before) that lower concentration of the NM caused higher biological impact. Data was deposited to ProteomeXchange, identifier PXD024444.

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 presence of antibiotics such as erythromycin, even in trace amounts, has long been acknowledged for negatively impacting ecosystems in freshwater environments. Although many studies have focused on the impact of antibiotic pollution at a macroecological level, the impact of erythromycin on microecosystems, such as freshwater biofilms, is still not fully understood. This knowledge gap may be attributed to the lack of robust multispecies biofilm models for fundamental investigations. Here, we used a lab-cultured multispecies biofilm model to elucidate the holistic response of a microbial community to erythromycin exposure using metagenomic and metabolomic approaches. Metagenomic analyses revealed that biofilm microbial diversity did not alter following erythromycin exposure. Notably, certain predicted metabolic pathways such as cell–cell communication pathways, amino acid metabolism, and peptidoglycan biosynthesis, mainly by the phyla Actinobacteria, Alpha/Beta-proteobacteria, Bacteroidetes, and Verrucomicrobia, were found to be involved in the maintenance of homeostasis-like balance in the freshwater biofilm. Further untargeted metabolomics data highlighted changes in lipid metabolism and linoleic acid metabolism and their related molecules as a direct consequence of erythromycin exposure. Overall, the study presented a unique picture of how multispecies biofilms respond to single environmental stress exposures. Moreover, the study demonstrated the feasibility of using lab simulated multispecies biofilms for investigating their interaction and reactivity of specific bioactive compounds or pollutants at a fundamental level.

Arsenic (As) is a ubiquitous metalloid that is highly toxic to all living organisms. When grown in As-contaminated soils, plants may accumulate significant amounts of As in the grains or edible shoot parts which then enter a food chain. Plant growth and development per se are also both affected by arsenic. These effects are traditionally attributed to As-induced accumulation of reactive oxygen species (ROS) and a consequent lipid peroxidation and damage to cellular membranes. However, this view is oversimplified, as As exposure have a major impact on many metabolic processes in plants, including availability of essential nutrients, photosynthesis, carbohydrate metabolism, lipid metabolism, protein metabolism, and sulfur metabolism. This review is aimed to fill this gap in the knowledge. In addition, the molecular basis of arsenic uptake and transport in plants and prospects of creating low As-accumulating crop species, for both agricultural productivity and food safety, are discussed.