Abstract 601: Nicotinic Acid Prevents and Restores Steatohepatitis Together with Amelioration of Postprandial Dyslipidemia.
Background and aims: ICR mouse neonatally administered with monosodium glutamate (MSG) shows obesity, insulin resistance, and is a murine model of steatohepatitis. We analysed the effect of nicotinic acid (niacin), an antilipidemic drug and also a potent lipolysis inhibitor.
Methods: Neonatal ICR mice were subcutaneously injected with 2 mg/g of MSG or saline at 5 consecutive days after birth and fed a normal chow. Niacin was administered by dietary supplementation (0.5% w/w) since 5 week-old. After 12 weeks, mice were sacrificed and tissue samples were collected. Niacin was also administered to 12 week-old mice already having steatosis for 12 weeks.
Results: After 12 weeks of treatment of niacin, MSG-treated mice showed less weight of body (21.5%, p < 0.001) and liver (52.5%, p < 0.001). Histopathological analyses showed markedly prevention of steatohepatitis. NAFLD activity scores (NAS) of niacin and vehicle groups were 0.0 +/- 0.0, 5.2 +/- 0.4, respectively (p < 0.01). Niacin also dramatically ameliorated accomplished steatohepatitis. Niacin treatment ameliorated dyslipidemia; atherogenic LDL fraction was disappeared in fasting plasma, and elevations of postprandial NEFA and triglycerides were suppressed. Hepatic gene expression of lipogenic genes was not decreased, while expression of Fsp27 was slightly (25%, p < 0.05) decreased. On the other hand, niacin-treated group showed postprandial hyperglycemia. Although there were no evidence of insulin resistance by insulin tolerance test and hepatic Akt phosphorylation, postprandial insulin response was impaired by niacin treatment.
Conclusion: Niacin prevented and ameliorated steatohepatitis together with amelioration of postprandial dyslipidemia at least partially due to inhibition of NEFA influx into the liver, although niacin impaired postprandial insulin response.
Author Disclosures: M. Hara: None. M. Kurano: None. K. Tsuneyama: None. K. Kikuchi: None. A. Takai: None. T. Matsushima: None. K. Tsukamoto: None.
- © 2014 by American Heart Association, Inc.