Dyslipidemia is a critical factor in the development of atherosclerosis and consequent cardiovascular disease. Numerous pieces of evidence demonstrate the association between air pollution and abnormal blood lipids. Although the results of epidemiological studies on the link between air pollution and blood lipids are unsettled due to different research methods and conditions, most of them corroborate the harmful effects of air pollution on blood lipids. Mechanism studies have revealed that air pollution may affect blood lipids via oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and hypothalamic hormone and epigenetic changes. Moreover, there is a risk of metabolic diseases associated with air pollution, including fatty liver disease, diabetes mellitus, and obesity, which are often accompanied by dyslipidemia. Therefore, it is biologically plausible that air pollution affects blood lipids. The overall evidence supports that air pollution has a deleterious effect on blood lipid health. However, further research into susceptibility, indoor air pollution, and gaseous pollutants is required, and the issue of assessing the effects of mixtures of air pollutants remains an obstacle for the future.

The liver is considered the major target organ affected by oral exposure to titanium dioxide nanoparticles (TiO₂ NPs), but the mechanism of hepatotoxicity is not fully understood. This study investigated the effect of TiO₂ NPs on the expression profile of long non-coding RNA (lncRNA) in hepatocytes and tried to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. The human hepatocellular carcinoma cells (HepG2) were treated with TiO₂ NPs at doses of 0–200 μg/mL for 48 h and then RNA sequencing was implemented. The differential lncRNAs between the control and TiO₂ NPs-treated groups were screened, then the lncRNA–mRNA network and enrichment pathways were analyzed via multivariate statistics. As a result, 46,759 lncRNAs were identified and 129 differential lncRNAs were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the targeted mRNAs of those differential lncRNAs were enriched in the Hedgehog signaling pathway, Vasopressin-regulated water reabsorption, and Glutamatergic synapse. Moreover, two lncRNA–mRNA networks, including lncRNA NONHSAT256380.1-JRK and lncRNA NONHSAT173563.1-SMIM22, were verified by mRNA detection. This study demonstrated that an alteration in the lncRNA expression profile could be induced by TiO₂ NPs and epigenetics may play an important role in the mechanism of hepatotoxicity.

(1) Background: Silica nanoparticles (SiO₂ NPs) have a high potential for human exposure and tend to accumulate in the liver. This study aimed to explore the size-dependent cytotoxicity induced by SiO₂ NPs and identify key molecular pathways at the in vitro level through proteomics, metabolomics, and a combination of multiple omics methods. (2) Methods: The human hepatoma cells (HepG2) cells were exposed to SiO₂ NPs of three different sizes (60, 250, and 400 nm) at doses of 0, 12.5, 25, 50, 100, and 200 μg/mL for 24 h. (3) Results: Exposure to 60 nm SiO₂ NPs induced more reduction in cell viability than the other two larger-scale particles. Changes in the metabolomic and proteomic profiles of HepG2 cells induced by SiO₂ NPs were also size-dependent. The main pathways that were significantly affected in the 60 nm SiO₂ NPs treatment group represented cholesterol metabolism in proteomics and central carbon metabolism in metabolomics. Moreover, common enrichment pathways between differential proteins and metabolites included protein digestion and absorption and vitamin digestion and absorption. (4) Conclusions: Exposure to SiO₂ NPs could induce size-dependent cytotoxicity and changes in proteomics and metabolomics, probably mainly by interfering with energy metabolism pathways.

Titanium dioxide nanoparticles (TiO₂ NPs), widely used as food additives, frequently coexist with high-fat diets (HD) in modern dietary patterns, yet their combined in vivo toxicity remains poorly understood. This study investigated the multi-organ effects of co-exposure to TiO₂ NPs or food-grade E171 and HD in male C57BL/6J mice. Mice were randomly assigned to six groups and fed regular or high-fat diets containing 1 wt% TiO₂ NPs or E171 for 13 weeks. Histopathology, serum biochemistry, organ coefficients, and open-field behavioral tests were used to assess tissue injury and functional alterations. Co-exposure to TiO₂ NPs and HD markedly exacerbated tissue damage across multiple organs. In the liver, more severe ballooning degeneration, necrosis, and inflammatory infiltration were observed, accompanied by altered liver enzymes and reduced organ coefficients. Intestinal injury was characterized by crypt distortion and increased inflammation, particularly in the HD + TiO₂ group. Testicular tissues showed disorganized seminiferous tubules, loss of spermatogenic cells, and interstitial hyperplasia. In the brain, hippocampal neurons exhibited pyknosis and disarray, with decreased brain coefficients and impaired exploratory behavior. E171 induced similar but milder effects. These findings indicate that HD enhances TiO₂ NPs induced multi-organ toxicity, highlighting the health risks of realistic co-exposure to dietary nanoparticles and high-fat foods.