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Translational Medical Research Commons™
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Articles 1 - 5 of 5
Full-Text Articles in Translational Medical Research
The Hiv Protease Inhibitor Saquinavir Impairs Lipid Metabolism And Glucose Transport In Cultured Adipocytes, S. Ranganathan, Philip A. Kern
The Hiv Protease Inhibitor Saquinavir Impairs Lipid Metabolism And Glucose Transport In Cultured Adipocytes, S. Ranganathan, Philip A. Kern
Clinical and Translational Science Faculty Publications
Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 μg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [14C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir …
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Clinical and Translational Science Faculty Publications
The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. …
Thiazolidinediones Inhibit Lipoprotein Lipase Activity In Adipocytes, Subramanian Ranganathan, Philip A. Kern
Thiazolidinediones Inhibit Lipoprotein Lipase Activity In Adipocytes, Subramanian Ranganathan, Philip A. Kern
Clinical and Translational Science Faculty Publications
The thiazolidinediones troglitazone and BRL 49653 improve insulin sensitivity in humans and animals with insulin resistance. Adipose tissue lipoprotein lipase is an insulin-sensitive enzyme. We examined the effects of thiazolidinediones on lipoprotein lipase expression in adipocytes. When added to 3T3-F442A, 3T3-L1, and rat adipocytes in culture, troglitazone and BRL 49653 inhibited lipoprotein lipase activity. This inhibition was observed at concentrations as low as 0.1 μM and within 2 h after addition of the drug. Lipoprotein lipase activity was inhibited in differentiated adipocytes as well as the differentiating cells. Despite this decrease in enzyme activity, these drugs increased mRNA levels in …
Translational Regulation Of Lipoprotein Lipase By Epinephrine Involves A Trans-Acting Binding Protein Interacting With The 3′ Untranslated Region, Gouri Ranganathan, Diane Vu, Philip A. Kern
Translational Regulation Of Lipoprotein Lipase By Epinephrine Involves A Trans-Acting Binding Protein Interacting With The 3′ Untranslated Region, Gouri Ranganathan, Diane Vu, Philip A. Kern
Clinical and Translational Science Faculty Publications
To better characterize the translational regulation of lipoprotein lipase (LPL) by epinephrine, cytoplasmic extracts were prepared from 3T3-L1 adipocytes, 3T3-F442A adipocytes, and other nonadipocyte cell lines (C2 cells, 3T3 fibroblasts, and Chinese hamster ovary cells). After treatment with epinephrine, cell extracts from the adipocytes inhibited LPL translation in an in vitro translation assay, whereas extracts from the C2 cells and 3T3 fibroblasts did not affect LPL translation. To identify the region on the LPL mRNA that controlled translation, in vitro translation was carried out using constructs containing different LPL sequences. Specific deletion of the first 50 (1601-1650) nucleotides of the …
1,25-Dihydroxyvitamin D Induces Lipoprotein Lipase Expression In 3t3-L1 Cells In Association With Adipocyte Differentiation, Diane Vu, John M. Ong, Thomas L. Clemens, Philip A. Kern
1,25-Dihydroxyvitamin D Induces Lipoprotein Lipase Expression In 3t3-L1 Cells In Association With Adipocyte Differentiation, Diane Vu, John M. Ong, Thomas L. Clemens, Philip A. Kern
Clinical and Translational Science Faculty Publications
1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is known to modulate the development of hone and other mesenchymal cell types. Since osteoblasts and adipocytes are thought to arise in bone marrow from a common progenitor, this work examined the effects of 1,25-(OH)2D3 on adipocyte development, and in particular on the expression of lipoprotein lipase (LPL), which is an early marker for the differentiated adipocyte. 3T3-L1 preadipocytes were cultured in the presence of 1.25-(OH)2D3 (10-9 to 10-7 M) for up to 7 days. LPL activity was measured in the medium and cell …