title: Pharmacological doses of niacin stimulate the expression of genes involved in carnitine uptake and biosynthesis and improve the carnitine status of obese Zucker rats.
abstract: BACKGROUND
  Activation of peroxisome proliferator-activated receptor (PPAR)α and PPARδ causes an elevation of tissue carnitine concentrations through induction of genes involved in carnitine uptake [novel organic cation transporter 2, (OCTN2)], and carnitine biosynthesis [γ-butyrobetaine dioxygenase (BBD), 4-N-trimethyl-aminobutyraldehyde dehydrogenase (TMABA-DH)]. Recent studies showed that administration of the plasma lipid-lowering drug niacin causes activation of PPARα and/or PPARδ in tissues of obese Zucker rats, which have a compromised carnitine status and an impaired fatty acid oxidation capacity. Thus, we hypothesized that niacin administration to obese Zucker rats is also able to improve the diminished carnitine status of obese Zucker rats through PPAR-mediated stimulation of genes involved in carnitine uptake and biosynthesis.
  
  
  METHODS
  To test this hypothesis, we used plasma, muscle and liver samples from a recent experiment with obese Zucker rats, which were fed either a niacin-adequate diet (30 mg niacin/kg diet) or a diet with a pharmacological niacin dose (780 mg niacin/kg diet), and determined concentrations of carnitine in tissues and mRNA and protein levels of genes critical for carnitine homeostasis (OCTN2, BBD, TMABA-DH). Statistical data analysis of all data was done by one-way ANOVA, and Fisher's multiple range test.
  
  
  RESULTS
  Rats of the obese niacin group had higher concentrations of total carnitine in plasma, skeletal muscle and liver, higher mRNA and protein levels of OCTN2, BBD, and TMABA-DH in the liver and higher mRNA and protein levels of OCTN2 in skeletal muscle than those of the obese control group (P < 0.05), whereas rats of the obese control group had lower concentrations of total carnitine in plasma and skeletal muscle than lean rats (P < 0.05).
  
  
  CONCLUSIONS
  The results show for the first time that niacin administration stimulates the expression of genes involved in carnitine uptake and biosynthesis and improves the diminished carnitine status of obese Zucker rats. We assume that the induction of genes involved in carnitine uptake and biosynthesis by niacin administration is mediated by PPAR-activation.
authors.forename: Aline
authors.initials: A
authors.lastname: Couturier
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35390 Giessen, Germany. robert.ringseis@ernaehrung.uni-giessen.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Ringseis
authors.forename: Erika
authors.initials: E
authors.lastname: Most
authors.forename: Klaus
authors.initials: K
authors.lastname: Eder
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002331:Carnitine / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D017931:DNA Primers; D015870:Gene Expression / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D000074058:Solute Carrier Family 22 Member 5; D050563:gamma-Butyrobetaine Dioxygenase / Q000235:genetics
chemical_list: D017931:DNA Primers; D027701:Organic Cation Transport Proteins; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D009525:Niacin; D050563:gamma-Butyrobetaine Dioxygenase; C023095:4-N-trimethylaminobutyraldehyde dehydrogenase; D000445:Aldehyde Oxidoreductases; D002331:Carnitine