Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.
The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apol...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1992-06-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520415093 |
| _version_ | 1818716098763161600 |
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| author | CM Arbeeny DS Meyers KE Bergquist RE Gregg |
| author_facet | CM Arbeeny DS Meyers KE Bergquist RE Gregg |
| author_sort | CM Arbeeny |
| collection | DOAJ |
| description | The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein. |
| first_indexed | 2024-12-17T19:13:52Z |
| format | Article |
| id | doaj.art-fb5a0a543871455282816e8fac0b7467 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T19:13:52Z |
| publishDate | 1992-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fb5a0a543871455282816e8fac0b74672022-12-21T21:35:48ZengElsevierJournal of Lipid Research0022-22751992-06-01336843851Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.CM Arbeeny0DS Meyers1KE Bergquist2RE Gregg3Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein.http://www.sciencedirect.com/science/article/pii/S0022227520415093 |
| spellingShingle | CM Arbeeny DS Meyers KE Bergquist RE Gregg Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. Journal of Lipid Research |
| title | Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. |
| title_full | Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. |
| title_fullStr | Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. |
| title_full_unstemmed | Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. |
| title_short | Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. |
| title_sort | inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520415093 |
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