Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease

被引:62
作者
Ganji, Shobha H.
Kukes, Gary D.
Lambrecht, Nils
Kashyap, Moti L.
Kamanna, Vaijinath S.
机构
[1] Dept Vet Affairs Healthcare Syst, Long Beach, CA USA
[2] Univ Calif Irvine, Irvine, CA USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2014年 / 306卷 / 04期
关键词
niacin; nicotinic acid; nonalcoholic fatty liver disease; hepatic steatosis; nonalcoholic steatohepatitis; INSULIN-RESISTANCE; VITAMIN-E; ADIPOSE-TISSUE; NICOTINIC ACID; STEATOHEPATITIS; MICE; DIET; PIOGLITAZONE; DGAT2; EXPRESSION;
D O I
10.1152/ajpgi.00181.2013
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Non-alcoholic 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.
引用
收藏
页码:G320 / G327
页数:8
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