Up-regulation of microRNA-367 promotes liver steatosis through repressing TBL1 in obese mice.

OBJECTIVE: Increasing evidence has demonstrated that microRNAs (miRNAs) play a critical role in the progression of metabolic disorders, including obesity-induced non-alcoholic fatty liver disease (NAFLD). In the present study, the expression and function of miR-367 were investigated. MATERIALS AND METHODS: C57BL/6 male mice aged 8 weeks were fed with a normal diet (ND) or high-fat-diet (HFD). The expression levels of miR-367 were analyzed in livers from two groups of mice by quantitative real-time PCR. Adenovirus containing miR-367 or negative control (NC) were constructed and administrated into C57BL/6 mice by tail vain injection. Potential targets of miR-367 were screened by miRWalk software and luciferase reporter assays. Mutagenesis analysis and Western blots were used to further determine the target of miR-367 in obese mice. RESULTS: We found that the expression of hepatic miR-367 was up-regulated in obese mice. In vitro and in vivo studies further demonstrated that overexpression of miR-367 mimics promoted triglyceride accumulation in cells and lean mice. At the molecular level, transducin beta-like 1 (TBL1), a coactivator of nuclear receptor peroxisome proliferator-activated receptor (PPAR) α, was identified as a direct target of miR-367. As a result, miR-367 overexpression resulted in an inhibition of fatty acid oxidation, leading to hepatosteatosis. CONCLUSIONS: Our data suggest miR-367/TBL1 regulatory pathway might have an important role for in the development of NAFLD.

[Regulatory role of calcium activated chloride channel in pulmonary vascular structural remodeling in rats with pulmonary arterial hypertension induced by high pulmonary blood flow].

OBJECTIVE: To explore the regulatory role of calcium activated chloride channel (CaCC) in vascular structural remodeling in pathogenesis of pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow. METHOD: An abdominal aorta and inferior vena cava shunting operation was used to induce high pulmonary blood flow and establish a PAH rat model.Seventy-five SD rats were randomly divided into normal, sham, shunt, niflumic acid (NFA) 1(0.2 mg/(kg·d))and NFA 2 (0.4 mg/(kg·d)) groups. There were 15 rats in each group. Pulmonary artery pressure and vascular structural remodeling were measured, arteriole contraction ratio among these groups were compared using vascular tone analysis system, and the electrophysiology of pulmonary artery smooth muscle cell (PASMC) was recorded using patch clamp technology. Differences between multiple groups were compared through variance analysis and that between groups with q test. RESULT: Compared with normal ((14.4±1.3 ) mmHg, 1 mmHg=0.133 kPa)and sham groups ((13.5±2.3 ) mmHg), mean pulmonary artery pressure in shunt group ((27.4±2.4 ) mmHg) increased significantly (P<0.05). Compared with shunt group, mean pulmonary artery pressure in NFA 1 group ((21.2±2.0) mmHg) and NFA 2 group ((22.3±2.0) mmHg) decreased significantly (P<0.05). Pulmonary vascular structural remodeling including pulmonary artery stenosis presented in shunt group. Compared with normal ((114.3±1.2)%) and sham ((115.5±1.1)%) groups, arteriole contraction ratio to 10(-5) mol/L phenylephrine in shunt group ((132.6±1.4)%) increased significantly (P<0.05). Compared with shunt group, pulmonary vascular structural remodeling alleviated in NFA 1 and NFA 2 groups. Arteriole contraction ratio in NFA 1 group ((126.4±1.3)%) and NFA 2 group ((124.6±1.0)%) decreased significantly compared with shunt group (P<0.05). Patch clamp technique recorded typical CaCC currents. Compared with normal ((32.3±2.3 ) pA/pF) and sham groups ((35.3±1.2) pA/pF), the CaCC current density of PASMC in shunt group ((51.3±2.7) pA/pF) increased significantly (P<0.05). Compared with shunt group, the CaCC current density of PASMC in NFA 1 group ((40.2±1.5 ) pA/pF) and NFA 2 group ((42.7±2.2) pA/pF) decreased significantly (P<0.05). CONCLUSION: CaCC is involved in pulmonary arterial hypertension induced by high pulmonary blood flow through regulating membrane potential. NFA attenuate pulmonary vascular structural remodeling and pulmonary pressure through decreasing CaCC current density of PASMC membrane.

Relationship between a lipoprotein lipase gene polymorphism in placental tissue and insulin resistance in patients with gestational diabetes mellitus.

The aim of this study was to investigate the relationship between a lipoprotein lipase (LPL) gene polymorphism in placental tissue and insulin resistance (IR) in patients with gestational diabetes mellitus. Using polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP) analysis, the LPL HindIII RFLP was examined in the placental tissue of 110 patients with gestational diabetes mellitus (observation group) and 110 women with normal gestation (control group). The relationships between fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting insulin (FINS), cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), body mass index (BMI), and IR indices and the LPL polymorphism in the two study groups and their offspring were determined. The frequency of the H+ allele was significantly higher in the observation group than in the controls (P < 0.05). There were statistically significant differences in the observation group between the FPG, PPG, LDL, TC, TG, HDL, BMI, FINS, and IR indices of the H+H+ group and those of the non H+H+ type patients (P < 0.05). Correlation analysis showed that the LPL gene polymorphism was positively related to IR. There were statistically significant differences between HDL, BMI, and IR indices between the two study groups (P < 0.05). In conclusion, the LPL gene polymorphism was determined to be the main factor related to IR in women with gestational diabetes, and was also found to be related to the IR of their offspring.

[Characteristics of CDDP-PLA microspheres in vitro and in vivo].

Studies on the drug release in vitro and hepatic arterial chemoembolization in vivo were carried out with the newly developed CDDP-PLA microspheres. The mechanism of the in vitro release was shown to conform to Higuchi equation. After chemoembolization the CDDP-PLA microspheres showed remarkably lower CDDP concentrations in the general circulation and much higher concentrations in the hepatic tissue e. g. up to 21.55 +/- 12.18 micrograms/g at 8 h, which is much higher than that (3.16 +/- 0.09 micrograms/g) of the CDDP in hepatic arterial infusions. Thus, the CDDP-PLA microspheres may improve the curative effects and lower the side effects, especially the kidney toxicity, of the anticancer drug cisplatin.