circ_0005379 inhibits the progression of oral squamous cell carcinoma by regulating the miR-17-5p/acyl-CoA oxidase 1 axis / 华西口腔医学杂志

OBJECTIVES@#To investigate the effects of circ_0005379 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells and its mechanism.@*METHODS@#Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0005379 and miR-17-5p in OSCC tissues and SCC15 cell lines. Western blot was used to detect the expression levels of acyl-CoA oxidase 1 (ACOX1). The circ_0005379 overexpression vector was transfected into SCC15 cells. Methyl thiazolyl tetrazolium blue staining, flow cytometry, Transwell, and Western blot were used to detect the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of SCC15 cells and the expression of E-cadherin, β-catenin, and Snail proteins. Dual luciferase reporter assay and RNA immunoprecipitation were used to examine the regulation of circ_0005379, miR-17-5p, miR-17-5p, and ACOX1 in SCC15 cells. A nude mouse xenograft model of SCC15 cells stably overexpressing circ_0005379 was established, and the effect of circ_0005379 overexpression on the growth of xenografts in nude mice was observed.@*RESULTS@#Compared with adjacent cancer tissues, the expression levels of circ_0005379 and ACOX1 proteins in OSCC tissues were decreased (@*CONCLUSIONS@#circ_0005379 may inhibit the proliferation, migration, and invasion of OSCC cells by downregulating the expression of miR-17-5p and upregulating ACOX1, which promote apoptosis and inhibit tumor growth

Leucrose, a Sucrose Isomer, Suppresses Hepatic Fat Accumulation by Regulating Hepatic Lipogenesis and Fat Oxidation in High-fat Diet-induced Obese Mice

Obesity is currently one of the most serious public health problems and it can lead to numerous metabolic diseases. Leucrose, d-glucopyranosyl-α-(1-5)-d-fructopyranose, is an isoform of sucrose and it is naturally found in pollen and honey. The aim of this study was to investigate the effect of leucrose on metabolic changes induced by a high-fat diet (HFD) that lead to obesity. C57BL/6 mice were fed a 60% HFD or a HFD with 25% (L25) or 50% (L50) of its total sucrose content replaced with leucrose for 12 weeks. Leucrose supplementation improved fasting blood glucose levels and hepatic triglyceride content. In addition, leucrose supplementation reduced mRNA levels of lipogenesis-related genes, including peroxisome proliferator-activated receptor γ, sterol regulatory element binding protein 1C, and fatty acid synthase in HFD mice. Conversely, mRNA levels of β oxidation-related genes, such as carnitine palmitoyltransferase 1A and acyl CoA oxidase, returned to control levels with leucrose supplementation. Taken together, these results demonstrated the therapeutic potential of leucrose to prevent metabolic abnormalities by mediating regulation of plasma glucose level and hepatic triglyceride accumulation.

Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice

In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of beta-oxidation-related genes, such as peroxisome proliferator-activated receptor alpha (PPAR-alpha), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid beta-oxidation in mice.

Oxidation of fatty acid may be enhanced by a combination of pomegranate fruit phytochemicals and acetic acid in HepG2 cells

We investigated whether the combination of phytochemicals and acetic acid in the form of fruit vinegar provides an additive effect on changes of mRNA levels related to fatty acid oxidation in human hepatocyte (HepG2). Among the seven fruit vinegars (Rubuscoreanus, Opuntia, blueberry, cherry, red ginseng, mulberry, and pomegranate) studied, treatment of HepG2 with pomegranate vinegar (PV) at concentrations containing 1 mM acetic acid showed the highest in vitro potentiating effect on the mRNA expression levels of peroxisome proliferator-activated receptor alpha, carnitinepalmitoyl transferase-1, and acyl-CoA oxidase compared to the control group (P < 0.05). Reversed-phase liquid chromatography in combination with quadrupole time-of-flight mass spectrometry analysis revealed four potential compounds (punicalagin B, ellagic acid, and two unidentified compounds) responsible for altered gene expression in HepG2 cells treated with PV as compared with the others. Further investigations are warranted to determine if drinking PV beverages may help to maintain a healthy body weight in overweight subjects.

Cellular oxidative stress and peroxisomal enzyme activities in pediatric liver transplant patients

In this study, we examined the activities of key peroxisomal enzymes in peripheral blood lymphocytes [PBLs] of pediatric liver transplant patients. Venous blood was drawn from 14 patients aged 5-16 years on FK-506 treatment and 18 healthy subjects for isolation of lymphocytes. Beta -Oxidation of very long chain fatty acids [VLCFAs] and activities of superoxide dismutase [SOD], glutathione peroxidase [GPx], NADPH oxidase [NOX], catalase and peroxisomal enzyme acyl CoA oxidase [ACO] were measured in cellular homogenates. Levels of malondialdehyde [MDA] were measured as an index of lipid peroxidation. Protein content and mRNA levels of catalase, peroxisomal membrane protein-70 [PMP-70] and ACO were measured using Western blotting and PCR techniques. PBLs isolated from liver transplant patients showed significantly [p < 0.01] increased levels [226.9 +/- 24.5 micro mol/mg protein] of MDA as compared to the levels in controls [162.8 +/- 19.6 micro mol/mg protein], whereas enzyme activities of SOD and NOX remained unaltered in patients' cells. Enzyme activities of catalase and GPx were markedly [p < 0.01] decreased in cells isolated from liver transplant patients. ACO activity and beta -oxidation of VLCFAs in PBLs from liver transplant patients were however found to be significantly increased by 38 and 52% respectively when compared with controls. Gene expression of PMP-70 and ACO was also significantly increased [p < 0.01] in PBLs of patients. Our results clearly showed that peroxisomal metabolic activities are markedly altered in lymphocytes of liver transplant patients and might contribute to the development of cellular oxidative stress

Effect of dietary protamine on lipid metabolism in rats

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid beta-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver beta-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.