HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.

Topical lovastatin stimulates epidermal fatty acid synthesis in vivo; therefore, studies were undertaken to examine the effects of HMG-CoA reductase inhibitors on fatty acid metabolism in cultured keratinocytes. When exposed to fluindostatin or lovastatin for greater than or equal to 24 h, keratinoc...

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Main Authors: ML Williams, GK Menon, KP Hanley
Format: Article
Language:English
Published: Elsevier 1992-02-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520415391
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spelling doaj-56b4a73aef4844be83820628e9275a722021-04-26T05:52:53ZengElsevierJournal of Lipid Research0022-22751992-02-01332193208HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.ML Williams0GK Menon1KP Hanley2Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121.Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121.Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121.Topical lovastatin stimulates epidermal fatty acid synthesis in vivo; therefore, studies were undertaken to examine the effects of HMG-CoA reductase inhibitors on fatty acid metabolism in cultured keratinocytes. When exposed to fluindostatin or lovastatin for greater than or equal to 24 h, keratinocytes in serum-free media accumulated nile red-fluorescent lipid droplets. By 72 h, the triacylglycerol and phospholipid content were increased 2.5- and 1.3-fold, respectively. Reductase inhibitors (1-10 microM) increased fatty acid synthesis approximately 1.5-fold; increased synthesis was noted only after greater than 15 h exposure and was distributed among phospholipids and triacylglycerols. Oxidation of [14C]palmitate to CO2 was decreased greater than 50% in inhibitor-treated cultures, and label accumulated in triacylglycerols. Inhibitor-treated keratinocytes exhibited increased numbers of peroxisomes, using diaminobenzidene ultracytochemistry. Peroxisomal hyperplasia was also demonstrated by increased catalase activity (1.5- to 2.5-fold), increased dihydroxyacetone phosphate acyltransferase activity (1.4-fold) and increased peroxisomal (KCN-insensitive) fatty acid oxidation (1.4-fold) in inhibitor-treated cultures. Thus HMG-CoA reductase inhibitors increase fatty acid synthesis, induce triacylglycol and phospholipid accumulation, and induce peroxisomes in cultured keratinocytes. Coincubations with either low density lipoproteins or 25-hydroxycholesterol prevented both the peroxisomal hyperplasia and increased fatty acid synthesis, suggesting that these effects of reductase inhibitors may be linked to their effects on the cholesterol biosynthetic pathway.http://www.sciencedirect.com/science/article/pii/S0022227520415391
collection DOAJ
language English
format Article
sources DOAJ
author ML Williams
GK Menon
KP Hanley
spellingShingle ML Williams
GK Menon
KP Hanley
HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
Journal of Lipid Research
author_facet ML Williams
GK Menon
KP Hanley
author_sort ML Williams
title HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
title_short HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
title_full HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
title_fullStr HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
title_full_unstemmed HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
title_sort hmg-coa reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes.
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 1992-02-01
description Topical lovastatin stimulates epidermal fatty acid synthesis in vivo; therefore, studies were undertaken to examine the effects of HMG-CoA reductase inhibitors on fatty acid metabolism in cultured keratinocytes. When exposed to fluindostatin or lovastatin for greater than or equal to 24 h, keratinocytes in serum-free media accumulated nile red-fluorescent lipid droplets. By 72 h, the triacylglycerol and phospholipid content were increased 2.5- and 1.3-fold, respectively. Reductase inhibitors (1-10 microM) increased fatty acid synthesis approximately 1.5-fold; increased synthesis was noted only after greater than 15 h exposure and was distributed among phospholipids and triacylglycerols. Oxidation of [14C]palmitate to CO2 was decreased greater than 50% in inhibitor-treated cultures, and label accumulated in triacylglycerols. Inhibitor-treated keratinocytes exhibited increased numbers of peroxisomes, using diaminobenzidene ultracytochemistry. Peroxisomal hyperplasia was also demonstrated by increased catalase activity (1.5- to 2.5-fold), increased dihydroxyacetone phosphate acyltransferase activity (1.4-fold) and increased peroxisomal (KCN-insensitive) fatty acid oxidation (1.4-fold) in inhibitor-treated cultures. Thus HMG-CoA reductase inhibitors increase fatty acid synthesis, induce triacylglycol and phospholipid accumulation, and induce peroxisomes in cultured keratinocytes. Coincubations with either low density lipoproteins or 25-hydroxycholesterol prevented both the peroxisomal hyperplasia and increased fatty acid synthesis, suggesting that these effects of reductase inhibitors may be linked to their effects on the cholesterol biosynthetic pathway.
url http://www.sciencedirect.com/science/article/pii/S0022227520415391
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