Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation.
This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholesterol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation.
Khedara
A
A
Department of Applied Biochemistry, Faculty of Applied Biological Science, Hiroshima University, Japan.
Kawai
Y
Y
Kayashita
J
J
Kato
N
N
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D004032:Diet; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood*
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides; D019335:Nitroarginine; D009569:Nitric Oxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase