Dietary nicotinic acid supplementation ameliorates chronic alcohol-induced fatty liver in rats

Alcohol Clin Exp Res. 2014 Jul;38(7):1982-92. doi: 10.1111/acer.12396. Epub 2014 May 21.

Abstract

Background: Alcohol abuse frequently causes niacin deficiency in association with the development of alcoholic liver disease. The objective of the present study was to determine whether dietary nicotinic acid (NA) deficiency exaggerates and whether dietary NA supplementation alleviates alcohol-induced fatty liver.

Methods: Male Sprague-Dawley rats were pair-fed with 4 isocaloric liquid diets: control, ethanol (EtOH), EtOH with dietary NA deficiency, and EtOH with dietary NA supplementation, respectively, for 8 weeks. The control and EtOH diets contained normal levels of NA (7.5 mg/l). Dietary NA deficiency (0 mg NA/l) was achieved by removing NA from the vitamin mix, while NA was added to the liquid diet at 750 mg/l for dietary NA supplementation.

Results: Chronic EtOH feeding induced significant lipid accumulation in the liver, which was not worsened by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Liver total NAD, NAD(+) , and NADH levels were remarkably higher in the NA supplemented group than the NA deficient or EtOH alone groups. Dietary NA supplementation to EtOH-fed rats increased the protein levels of hepatic cytochrome P450 4A1 (CYP4A1) and acyl-coenzyme A oxidase 1 without affecting their mRNA levels. Interestingly, we found dietary NA supplementation reduced the ubiquitination level of CYP4A1. In addition, hepatic fatty acid synthase expression was reduced, while the serum β-hydroxybutyrate and adiponectin concentrations were significantly elevated by dietary NA supplementation. Moreover, dietary NA supplementation modulated EtOH-perturbed liver and serum metabolite profiles.

Conclusions: These results demonstrate that alcoholic fatty liver was not exaggerated by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Increased hepatic fatty acid oxidation and decreased hepatic de novo lipogenesis contribute to the effects of dietary NA supplementation.

Keywords: Alcoholic Fatty Liver; Lipid Metabolism; Nicotinic Acid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Acyl-CoA Oxidase / metabolism
  • Adiponectin / blood
  • Animals
  • Chronic Disease
  • Cytochrome P-450 CYP4A / metabolism
  • Diet
  • Dietary Supplements*
  • Ethanol / antagonists & inhibitors
  • Ethanol / toxicity*
  • Fatty Acid Synthase, Type I / biosynthesis
  • Fatty Liver, Alcoholic / blood
  • Fatty Liver, Alcoholic / diet therapy*
  • Fatty Liver, Alcoholic / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Metabolomics
  • NAD / metabolism
  • Niacin / administration & dosage*
  • Niacin / deficiency
  • Niacin / therapeutic use*
  • Rats
  • Ubiquitination / drug effects

Substances

  • Adiponectin
  • NAD
  • Niacin
  • Ethanol
  • Cytochrome P-450 CYP4A
  • Acyl-CoA Oxidase
  • Fatty Acid Synthase, Type I
  • 3-Hydroxybutyric Acid