High Sodium Intake, as Assessed by Urinary Sodium Excretion, Is Associated with Nonalcoholic Fatty Liver Disease or Sarcopenia

Background/Aims@#We explored whether high sodium intake, assessed by urinary excretion, determines the risk of sarcopenia and nonalcoholic fatty liver disease (NAFLD). @*Methods@#We analyzed 10,036 adult participants with normal kidney function from the Korea National Health and Nutrition Examination Survey (2008–2011). NAFLD was identified using the fatty liver index, and the muscle mass was evaluated using dual X-ray absorptiometry. The dietary sodium intake was estimated using Tanaka’s equation. @*Results@#The mean 24-hour urinary sodium excretion was 144.2±36.1 mmol/day (corresponding to 3.3 g/day Na) in the total population. The 24-hour urinary sodium excretion showed moderate accuracy in predicting NAFLD (area under the receiver operating characteristic, 0.702; 95% confidence interval [CI], 0.692 to 0.712). A cutoff value of 99.96 mmol/day (corresponding to 2.30 g/day Na) for urinary sodium excretion in predicting NAFLD showed 76.1% sensitivity and 56.1% specificity. The results of multiple adjusted models indicated that the participants with the highest urinary sodium excretion had a significantly higher risk of NAFLD (odds ratio, 1.46; 95% CI, 1.27 to 1.66; p<0.001) and sarcopenia (odds ratio, 1.49; 95% CI, 1.28 to 1.73; p<0.001) than those with the lowest urinary sodium excretion. The association between a higher 24-hour urinary sodium excretion and NAFLD was independent of sarcopenia. @*Conclusions@#Participants with a high sodium intake, as assessed by sodium excretion, had a substantial risk of NAFLD and sarcopenia

Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells

Background@#Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study. @*Methods@#In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver. @*Results@#Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis. @*Conclusion@#Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

Recent Insights into Insulin-Like Growth Factor Binding Protein 2 Transcriptional Regulation

Insulin-like growth factor binding proteins (IGFBPs) are major regulators of insulin-like growth factor bioavailability and activity in metabolic signaling. Seven IGFBP family isoforms have been identified. Recent studies have shown that IGFBPs play a pivotal role in metabolic signaling and disease, including the pathogenesis of obesity, diabetes, and cancer. Although many studies have documented the various roles played by IGFBPs, transcriptional regulation of IGFBPs is not well understood. In this review, we focus on the regulatory mechanisms of IGFBP gene expression, and we summarize the findings of transcription factor activity in the IGFBP promoter region.

Identification and characterization of peroxisome proliferator response element in the mouse GLUT2 promoter

In the present study, we show that the expression of type 2 glucose transporter isoform (GLUT2) could be regulated by PPAR-gamma in the liver. Rosiglitazone, PPAR-gamma agonist, activated the GLUT2 mRNA level in the primary cultured hepatocytes and Alexander cells, when these cells were transfected with PPAR-gamma/RXR-alpha. We have localized the peroxisome proliferator response element in the mouse GLUT2 promoter by serial deletion studies and site-directed mutagenesis. Chromatin immunoprecipitation assay using ob/ob mice also showed that PPAR-gamma rather than PPAR-alpha binds to the -197/-184 region of GLUT2 promoter. Taken together, liver GLUT2 may be a direct target of PPAR-gamma ligand contributing to glucose transport into liver in a condition when PAPR-gamma expression is increased as in type 2 diabetes or in severe obesity.

HNF1 and/or HNF3 may contribute to the tissue specific expression of glucokinase gene

A possible role of hepatocyte nuclear factor 1 (HNF1) or HNF3, a predominant trans-acting factors of hepatic or pancreatic beta-cells, was examined on the tissue specific interdependent expression of glucokinase (GK) in liver, H4IIE, HepG2, HIT-T15 and MIN6 cell line. The tissues or cell lines known to express GK showed abundant levels of HNF1 and HNF3 mRNA as observed in liver, H4IIE, HepG2, HIT-T15 and MIN6 cells, whereas they were not detected in brain, heart, NIH 3T3, HeLa cells. The promoter of glucokinase contains several HNF3 consensus sequences and are well conserved in human, mouse and rat. Transfection of the glucokinase promotor linked with luciferase reporter to liver or pancreatic beta cell lines showed high interacting activities with HNF1 and HNF3, whereas minimal activities were detected in the cells expressing very low levels of HNFs. The binding of HNF1 or HNF3 to the GK promoter genes was confirmed by electrophoretic mobility shift assay (EMSA). From these data, we propose that the expression of HNF1 and/or HNF3 may, in part, contribute to the tissue specific expression of GK.