Sea fish contain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) which have been found to reduce triglyceride (TG) levels. However, sea fish may contain pollutants such as mercury which cause oxidative stress and increase TG levels. Therefore, the relationship between sea fish and TG remains unclear. We aimed to explore whether blood mercury (BHg) can affect the effect of sea fish consumption frequency on TG level among Chinese adults. A total of 10,780 participants were included in this study. BHg levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). The associations of sea fish consumption frequency with BHg and TG levels as well as the association of BHg with TG levels were evaluated using multiple linear regression. Causal mediation analysis was used to evaluate the mediation effect of BHg levels on the association of sea fish consumption frequency with TG levels. The frequency of sea fish consumption showed a negative association with TG level. Compared with the participants who never ate sea fish, the TG level decreased by 0.193 mmol/L in those who ate sea fish once a week or more [β (95%CI): −0.193 (−0.370, −0.015)]. Significant positive associations were observed of BHg with TG levels. With one unit increase of log2-transformed BHg, the change of TG level was 0.030 mmol/L [0.030 (0.009, 0.051)]. The association between sea fish consumption and TG was mediated by log2-transformed BHg [total effect = −0.037 (−0.074, −0.001); indirect effect = 0.009 (0.004, 0.015)], and the proportion mediated by log2-transformed BHg was 24.25%. BHg may reduce the beneficial effect of sea fish consumption frequency on TG levels among Chinese adults. Overall, sea fish consumption has more benefits than harms to TG.

Finding the potential environmental obesogens is crucial to explain the prevalence of obesity and the related pathologies. Increasing evidence has showed that many chemicals with endocrine disrupting effects can disturb lipid metabolism. Whether 4-hexylphenol (4-HP), a widely-used surfactant and a potential endocrine disrupting chemical (EDC), is associated to influence adipogenesis and hepatic lipid accumulation remained to be elucidated. In this study, both the 3T3-L1 differentiation model and oleic acid (OA)-treated HepG2 cells were used to investigate the effects of 4-HP on lipid metabolism, and the underlying estrogen receptor (ER)-involved mechanism was explored using MVLN assay, molecular docking simulation and the antagonist test. The results based on lipid droplet staining and triglyceride accumulation assay showed that 4-HP treatment promoted the adipogenic differentiation of 3T3-L1 cells and increased hepatic cellular OA accumulation in exposure concentration-dependent manners. The study on the elaborated transcription networks indicated that 4-HP activated peroxisome proliferator-activated receptor γ (PPARγ) as well as the subsequent adipogenic gene program in 3T3-L1 cells. This chemical also induced the increase of OA uptake and decreases of de novo lipogenesis and fatty acid oxidation in HepG2 cells. The agonistic activity of 4-HP in triggering ER-mediated pathway was shown to correlate with its perturbation in lipid metabolism, as evidenced by the enhanced development of mature lipid-laden adipocytes and suppression of excessive hepatic lipid accumulation upon its co-treatment with ER antagonist. Altogether, these findings provide new insights into the potential health impacts of 4-HP exposure as it may relate to obesity and nonalcoholic fatty liver disease.

Wild fish living downstream of wastewater treatment plants (WWTPs) often have increased body condition factors or body mass indices compared to upstream fish. This observation has been largely attributed to increased nutrient loading and food availability around wastewater effluent outflows. While a higher condition factor in fish is generally considered a predictor of healthy ecosystems, the metabolic status and capacity of the animals downstream of WWTPs may be a better predictor of fitness and potential population level effects. To address this, we sampled wild longnose dace (Rhinichthys cataractae), a native species in North American waterways, from sites upstream and downstream of WWTPs. Downstream fish had higher body mass indices, which corresponded with higher nutrient (lipid, protein, and glycogen) storage in somatic tissues compared to upstream fish. Liver transcriptome analysis revealed metabolic reprogramming favoring lipid synthesis, including higher hepatic triglyceride levels and transcript abundance of targeted lipogenic genes. This suggests that effluent exposure-mediated obesity in dace is a result of changes at the transcriptional level. To determine potential ecological consequences, we subjected these fish to an acute stressor in situ to determine their stress performance. Downstream fish failed to mobilize metabolites post-stress, and showed a reduction in liver aerobic and anaerobic metabolic capacity. Taken together, fish living downstream of WWTPs exhibit a greater lipid accumulation that results in metabolic disruption and may compromise the ability of these fish to cope with subsequent environmental and/or anthropogenic stressors.

Despite growing concern about the occurrence of microplastics in aquatic ecosystems there is only rudimentary understanding of the pathways through which any adverse effects might occur. Here, we assess the effects of polystyrene microplastics (PS-MPs; <70 μm) on a common and widespread algal species, Chlorella sorokiniana. We used laboratory exposure to test the hypothesis that the lipids and fatty acids (FAs) are important molecules in the response reactions of algae to this pollutant. Cultivation with PS-MPs systematically reduced the concentration of essential linoleic acid (ALA, C18:3n-3) in C. sorokiniana, concomitantly increasing oleic acid (C18:1n-9). Among the storage triacylglycerols, palmitoleic and oleic acids increased at the expenses of two essential fatty acids, linoleic (LIN, C18:2n-6) and ALA, while PS-MPs had even more pronounced effects on the fatty acid and hydrocarbon composition of waxes and steryl esters. The FA composition of two major chloroplast galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), were affected implying changes in the conformational structure of photosynthetic complexes in ways that can impair the photosynthesis. These data reveal how exposure to polystyrene microplastics can modify the concentrations of lipid molecules that are important intrinsically in cell membranes, and hence the lipid bilayers that could form an important barrier between algal cellular compartments and plastics in the aquatic environment. Changes in lipid synthesis and fatty acid composition in algae could also have repercussions for food quality, growth and stressor resistance in primary consumers. We advocate further studies of microplastics effects on the lipid composition of primary producers, and of their potential propagation through aquatic food webs.

Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentration-dependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development.

Environmental chemical exposures have been implicated as risk factors for the development of non-alcoholic fatty liver (NAFLD). Bisphenol S (BPS), widely used in multitudinous consumer products, could disrupt lipid metabolism in the liver. This study aimed at examining the hypothesis that long-term exposure to BPS promotes the development of liver fibrosis and inflammation by means of the application of a semi-static exposure experiment that exposed zebrafish to 1, 10, and 100 μg/L BPS from 3 h post fertilization to 120 day post fertilization. Results showed that the 120-d BPS exposure elevated plasma aspartate aminotransferase and alanine aminotransferase activities, increased triacylglycerol (TAG) and total cholesterol levels in male liver, and even induced hepatic apoptosis and fibrosis. Hepatic lipid accumulation observed in the 30-d BPS-exposed zebrafish was recovered after a 90-d depuration phase, thereby indicating that long-term BPS exposure promotes the progression of simple steatosis to non-alcoholic steatohepatitis. Furthermore, BPS exposure for 120-d promoted the synthesis of TAG and lipotoxic free fatty acids by elevating the transcription of srebp1, acc, fasn, and elovl6, induced endoplasmic reticulum (ER) stress with increasing expression levels of unfolded protein response (UPR) genes (perk, hsp5, atf4a, and ddit3), and then stimulated the expression of two key autophagy genes (atg3 and lc3) and inflammatory genes (il1b and tnfα). It is indicated that BPS can induce the development of steatohepatitis via the activation of the PERK-ATF4a pathway of the UPR. Data gathered suggest that environmental pollutants-induced ER stress with the activation of UPR can potentially trigger the NAFLD development in males. Overall, our study provided new sights into understanding of the adverse health effects of metabolism disrupting chemicals.

Adverse health effects of exposure to air pollution have been investigated in many previous studies. However, there is no study available on the association between maternal exposure to air pollution during pregnancy and cord blood lipid profile. This study, based on 150 mother-newborn pairs residing in Sabzevar, Iran (2018), evaluated the association of exposure to ambient air pollution as well as traffic indicators (total street length in different buffers around residential address and distance to major roads) during entire pregnancy with lipid levels cord blood lipid profile. Concentrations of PM₁₀, PM₂.₅, and PM₁ at maternal residential address were estimated using land use regression (LUR) models. We measured triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) levels and TC/HDL-C and TAG/HDL-C ratio in the cord blood samples to characterize their lipid profile. Multiple linear regression models were developed to estimate the association of exposure to air pollution and traffic indicators with cord blood lipid profile controlled for relevant covariates. Higher concentrations of PM₂.₅ and PM₁₀ were associated with higher levels of TAG, TC, HDL-C, TC/HDL-C, and TAG/HDL-C in cord blood samples. Moreover, higher concentration of PM₁ was associated with higher levels of TAG, TC and LDL-C. There was also a positive association between total street length in 100 m buffer around home and serum levels of TC, TAG, LDL-C and TC/HDL ratio (β = 3.73, 95% confidence intervals (CI): 1.76, 5.71; β = 2.75, 95% CI: 0.97, 4.53; β = 1.87, 95% CI: 0.64, 3.09; β = 0.06, 95% CI: 0.01, 0.11, respectively). However, the associations for total street length in larger buffers and distance to major roads were not statistically significant. Our findings support a relationship between exposure to air pollution during pregnancy and increase in cord blood lipid levels.

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.

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.

Metabolic syndrome is an important risk factor for non-communicable diseases, particularly type 2 diabetes, coronary heart disease, and stroke. Long-term exposure to greenspace could be protective of metabolic syndrome, but evidence for such an association is lacking. Accordingly, we investigated the association between long-term exposure to greenspace and risk of metabolic syndrome.The present longitudinal study was based on data from four clinical examinations between 1997 and 2013 in 6076 participants of the Whitehall II study, UK (aged 45–69 years at baseline). Long-term exposure to greenspace was assessed by satellite-based indices of greenspace including Normalized Difference Vegetation Index (NDVI) and Vegetation Continuous Field (VCF) averaged across buffers of 500 and 1000 m surrounding the participants’ residential location at each follow-up. The ascertainment of metabolic syndrome was based on the World Health Organization (WHO) definition. Hazard ratios for metabolic syndrome were estimated using Cox proportional hazards regression models, controlling for age, sex, ethnicity, lifestyle factors, and socioeconomic status.Higher residential surrounding greenspace was associated with lower risk of metabolic syndrome. An interquartile range increase in NDVI and VCF in the 500 m buffer was associated with 13% (95% confidence interval (CI): 1%, 23%) and 14% (95% CI: 5%, 22%) lower risk of metabolic syndrome, respectively. Greater exposure to greenspace was also associated with each individual component of metabolic syndrome, including a lower risk of high levels of fasting glucose, large waist circumference, high triglyceride levels, low HDL cholesterol, and hypertension. The association between residential surrounding greenspace and metabolic syndrome may have been mediated by physical activity and exposure to air pollution.The findings of the present study suggest that middle-aged and older adults living in greener neighbourhoods are at lower risk of metabolic syndrome than those living in neighbourhoods with less greenspace.