Feeding the nitric oxide synthase inhibitor L-NÏnitroarginine elevates serum very low density lipoprotein and hepatic triglyceride synthesis in rats
Abstract
This study was conducted to study the influence of dietary L-N(omega)nitroarginine (L-NNA), a nitric oxide (NO) synthase inhibitor, on serum lipids and lipoproteins and on the activities of enzymes related to lipid metabolism in rats. Feeding rats a diet containing 0.2 g/kg L-NNA for 5 weeks elevated serum concentrations of triglyceride, cholesterol, phospholipid, and free fatty acid and reduced serum nitrate (an oxidation product of NO). The elevation in serum triglyceride was mainly due to the elevation in very low density lipoprotein (VLDL) triglyceride. Contents of cholesterol and phospholipid in the VLDL fraction also were elevated by L-NNA. L-NNA treatment caused significantly higher activity of hepatic microsomal phosphatidate phosphohydrolase (the rate-limiting enzyme in triglyceride synthesis) and lower activity of hepatic carnitine palmitoyltransferase (the rate-limiting enzyme in fatty acid oxidation). Activities of hepatic enzymes responsible for fatty acid synthesis such as glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase were unaffected by L-NNA. The activity of hepatic microsomal phosphocholine cytidyltransferase (the rate-limiting enzyme in phosphatidylcholine synthesis) was reduced significantly by L-NNA. Our results suggest that lower NO production caused the elevations in hepatic triglyceride synthesis by higher esterification of fatty acid and lower fatty acid oxidation, leading to an enrichment of VLDL triglyceride.
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NO inhibits fatty acid synthesis in hepatocytes.
“Interestingly, NO also inhibits fatty acid synthesis in hepatocytes [341]”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [341]
In isolated hepatocytes, treatment with NO donors increases fatty acid oxidation in a cGMP-dependent manner by inhibiting acetyl CoA carboxylase and stimulating carnitine palmitoyl transferase activity.
“In isolated hepatocytes, treatment with NO donors was shown to increase fatty acid oxidation in a cGMP-dependent manner by inhibiting acetyl CoA carboxylase (thereby decreasing production of malonyl CoA) and by stimulating carnitine palmitoyl transferase activity [341].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [341]
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- Authors
- Goto, T.
- Affiliations
- Hiroshima University (JP)
- Corresponding author
- Goto, T
- ORCID
- Goto, T
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 10
- Issue
- 5
- Pages
- 274-278
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2121516307
- Cited by
- 17
- References
- 34
- Citations by year
- 2021: 1 · 2020: 2 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 1 · 2012: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- nitric oxide synthase inhibition, nitric oxide, VLDL, hepatic triglyceride synthesis, serum lipids, serum cholesterol, phosphatidate phosphohydrolase, carnitine palmitoyltransferase, fatty acid oxidation, phosphatidylcholine synthesis, dietary supplementation, lipid metabolism
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