ETC-1002 Reduces Blood Pressure in Hypercholesterolemic Patients with Mildly Elevated Blood Pressure

Abstract

Methods: Normal human primary hepatocytes (Lonza Walkersville Inc.) were first incubated with palmitic acid (0.5 mM) for 24 h to induce fat accumulation. Cells were then treated with niacin (0-0.5 mM) for 24 h. Cellular fat accumulation and formation of reactive oxygen species (ROS, as an index of oxidative stress) were measured by staining with Nile Red O and DCFDA fluorescence respectively. In-vivo effect of niacin on prevention and regression of hepatic steatosis was assessed in high-fat fed rat model of NAFLD. The histology of liver tissue from animals was examined in paraffin embedded hematoxylin and eosin (H&E) stained sections. Results: Niacin (at 0.25 and 0.5 mM doses) significantly inhibited palmitic acid-induced fat accumulation in hepatocytes by 45-62%. This effect was associated with robust inhibition of diacylglycerol acyltransferase 2 (DGAT2) mRNA expression by niacin. Niacin, in a dose-dependent manner, significantly inhibited ROS production in hepatocytes. In experimental rat model of NAFLD, inclusion of niacin at 0.5% and 1% in the high-fat diet significantly decreased liver fat content, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the high-fat diet significantly regressed steatosis. Conclusion: These novel findings suggest that niacin, through inhibiting hepatocyte fat accumulation and lipid peroxidation products, effectively prevents and causes the regression of hepatic steatosis and NAFLD. Clinical development of niacin formulations and niacin-related compounds for the treatment of NAFLD may offer a very cost-effective opportunity in addressing the unmet need for the development of therapeutic agents for NAFLD and other fatty liver disease. N PBO (95% CI) p-value