Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

Transforming growth factor-beta1 (TGF-beta1) is a growth factor that is implicated in fibrosis of many organs. The purpose of this study was to determine the sequential levels of TGF-beta1 in the pleural fluid of rabbits that had undergone empyema induction, as fibrosis of the pleural space develops. Thirty-seven rabbits underwent empyema induction. Rabbits were sacrificed on Days 1, 2, 3, 4, 5, 6, and 8. Pleural fluid and viscera pleura specimens were collected at autopsy. TGF-beta1 levels were measured in pleural fluid using a commercially available ELISA kit, and pathologic specimens were scored for evidence of fibrosis (pleural thickness and number of fibroblasts). The median levels of pleural fluid TGF-beta1 increased from 8,100 pg/ml (Days 1 and 2) to 39,600 pg/ml (Day 8). Pleural fluid TGF-beta1 levels closely correlated with microscopic pleural thickness (r = 0.7, p < 0.001) and number of fibroblasts present in the visceral pleura (r = 0.68, p < 0.001). The first increase in pleural fluid levels of TGF-beta1 (Day 3) occurred before the increase in pleural thickness (Day 4) and before the increase in number of fibroblasts (Day 4). In conclusion, pleural fluid levels of TGF-beta1 rise in experimental empyema as pleural fibrosis develops. The rise in empyemic pleural fluid TGF-beta1 levels correlates with markers of pleural space fibrosis.

No abstract