Plasminogen activator inhibitor-1 is independently associated with non-alcoholic fatty liver disease whereas leptin and adiponectin vary between genders.

BACKGROUND AND AIM: Alterations of adipocytokine levels and clinical parameters in non-alcoholic fatty liver disease (NAFLD) are crucial for the prognosis and complications of the diseases. However, the key adipocytokines independently associated with NAFLD have not been identified, and we aimed to investigate them. METHODS: This study was conducted on a consecutive series of 210 Taiwanese NAFLD patients and 420 sex- and age-matched controls. Fatty liver was diagnosed by magnetic resonance spectroscopy. The enrolled subjects' body mass indexes, homeostasis model of assessment-insulin resistance, uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, blood pressure, metabolic syndrome (yes/no), alanine aminotransferase, aspartate aminotransferase-to-platelet ratio indexes, leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were analyzed to determine their association with NAFLD. RESULTS: Univariate analysis showed that all of the aforementioned factors were associated with NAFLD, whereas multivariate analysis revealed that only PAI-1 (odds ratio: 1.39, P = 0.039) was independently associated with NAFLD. Subgroup analysis showed that females consistently had higher leptin (P < 0.001) and adiponectin (P < 0.001) levels than males, whereas their PAI-1 levels were similar. Males with NAFLD had higher leptin but lower adiponectin levels than their subgroup counterparts (all P < 0.001). Among the female subgroups, hyperleptinemia and hypoadiponectinemia were only observed in the NAFLD patients ≥ 45 years. CONCLUSIONS: PAI-1 is independently associated with NAFLD after adjusting for other factors, including leptin and adiponectin. Male and female NAFLD patients show distinct patterns of leptin and adiponectin alterations; special attention is required when evaluating these alterations in female NAFLD patients < 45 years.

Hydrodynamics-based transfection of the combination of betacellulin and neurogenic differentiation 1 DNA ameliorates hyperglycemia in mice with streptozotocin-induced diabetes.

BACKGROUND: The biohazards caused by the viral delivery of pancreatic transcription factors, including neurogenic differentiation 1 (Neurod1) and Betacellulin (Btc), to the murine liver limit application of this procedure in reversing diabetes. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Neurod1 and Btc in improving hyperglycemia. METHODS: Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the combination of Neurod1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Neurod1, and Btc-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Btc. Hepatic delivery of a combination of pcDNA-Neurod1 and pcDNA-Btc (experimental group) or pcDNA (control group) to mice with streptozocin-induced diabetes was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed. RESULTS: On day 3 after transfection, the transfection efficiencies of pcDNA-Btc and pcDNA-Neurod1 in the Hepa1-6 cells were 20% and 8%, respectively; respective values in the mouse livers were 30% and 10%. At 1 week after HBT, aside from hepatic expression of insulin, the experimental mice had a significantly lower sugar level (8-14 days after HBT, P values ranged from 0.034 to <0.001) than the control mice; the difference remained for 1 week but diminished afterward. The ALT levels and the body weight change were not different between the two groups. No mortality was noted in both groups. CONCLUSIONS: The hypoglycemic effect of Neurod1 and Btc delivered by HBT was transient and associated with negligible complications. In studies on the short-term hypoglycemic effects of Neurod1 and Btc in vivo, HBT is a potential alternative to viral delivery of Neurod1 and Btc to the murine liver.

Hydrodynamics-based transfection of pancreatic duodenal homeobox 1 DNA improves hyperglycemia and is associated with limited complications in diabetic mice.

The biohazards caused by the viral delivery of pancreatic duodenal homeobox gene 1 (Pdx1) to the murine liver limits its application. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Pdx1 in improving hyperglycemia. Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the Pdx1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Pdx1. Hepatic delivery of pcDNA-Pdx1 or pcDNA in streptozocin- induced diabetic mice was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed. On the 3(rd) day after transfection, the transfection efficiency in the Hepa1-6 cells and the mice livers was 5% and 0.35 %, respectively. At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 +/- 61.6 vs. 413 +/- 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. No significant difference in the ALT levels was observed between the 2 groups. No mortality was noted in the mice transfected with pcDNA-Pdx1. The hypoglycemic effect of Pdx1 delivered by HBT was transient and associated with negligible complications. In studies on the short-term biological effects of Pdx1 in vivo, HBT is a potential alternative to viral delivery of Pdx1 to the murine liver.