Solute carrier family 2 member 1 is involved in the development of nonalcoholic fatty liver disease.

UNLABELLED: Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of the present study was to identify genetic variants that could help to prognose and further understand the genetics and development of NAFLD. Allele frequencies of 3,072 single-nucleotide polymorphisms (SNPs) in 92 genes were characterized in 69 NAFLD patients and 217 healthy individuals. The markers that showed significant allele-frequency differences in the pilot groups were subsequently studied in 451 NAFLD patients and 304 healthy controls. Besides this, 4,414 type 2 diabetes mellitus (T2DM) cases and 4,567 controls were genotyped. Liver expression of the associated gene was measured and the effect of its potential role was studied by silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and the consequences of oleic acid (OA)-enriched medium on lipid accumulation in siSLC2A1-THLE2 cells were studied by gene-expression analysis, dihydroethidium staining, BODIPY, and quantification of intracellular triglyceride content, respectively. Several SNPs of SLC2A1 (solute carrier family 2 [facilitated glucose transporter] member 1) showed association with NAFLD, but not with T2DM, being the haplotype containing the minor allele of SLC2A1 sequence related to the susceptibility to develop NAFLD. Gene-expression analysis demonstrated a significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional analyses of transcriptome profiles drove us to demonstrate that in vitro silencing of SLC2A1 induces an increased OS activity and a higher lipid accumulation under OA treatment. CONCLUSIONS: Genetic variants of SLC2A1 are associated with NAFLD, and in vitro down-regulation of this gene promotes lipid accumulation. Moreover, the oxidative response detected in siSLC2A1-THLE2 cells corroborated the antioxidant properties previously related to this gene and linked the most representative clinical characteristics of NAFLD patients: oxidative injury and increased lipid storage.

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry.

PURPOSE: To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe3O4 lipophilic nanoparticles. MATERIALS AND METHODS: WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe3O4 nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland-Altman plots were produced; P values <0.05 were considered significant. RESULTS: In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 µmol·g⁻¹ and 5.9 µmol·g⁻¹, respectively, in the tumors, and 19.0 µmol ·g⁻¹ and 11.7 µmol·g⁻¹, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 µmol·g⁻¹ and 9.4 µmol · g⁻¹, respectively, in the tumors, and 115.3 µmol·g⁻¹ and 11.6 µmol·g⁻¹, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially in the tumors. CONCLUSION: ICP-MS demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful for quantifying the [Fe] in the different tissues in the CG animals, but not in the IG animals. Although the irregular distribution of nanoparticles caused an important bias in the measurements obtained by MRI, the relative increase in iron content inside the tumor was suggested.