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Articles 1 - 11 of 11
Full-Text Articles in Translational Medical Research
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression. Because the 3′-untranslated region (UTR) is involved in LPL translational regulation, transgenic mice were generated with adipose tissue expression of an LPL construct either with or without the proximal 3′-UTR and driven by the aP2 promoter. Both transgenic mouse colonies were viable and expressed the transgene, resulting in a 2-fold increase in LPL activity in white adipose …
The Translational Regulation Of Lipoprotein Lipase By Epinephrine Involves An Rna Binding Complex Including The Catalytic Subunit Of Protein Kinase A, Gouri Ranganathan, Dan Phan, Irina D. Pokrovskaya, Joan E. Mcewen, Chunling Li, Philip A. Kern
The Translational Regulation Of Lipoprotein Lipase By Epinephrine Involves An Rna Binding Complex Including The Catalytic Subunit Of Protein Kinase A, Gouri Ranganathan, Dan Phan, Irina D. Pokrovskaya, Joan E. Mcewen, Chunling Li, Philip A. Kern
Clinical and Translational Science Faculty Publications
The balance of lipid flux in adipocytes is controlled by the opposing actions of lipolysis and lipogenesis, which are controlled primarily by hormone-sensitive lipase and lipoprotein lipase (LPL), respectively. Catecholamines stimulate adipocyte lipolysis through reversible phosphorylation of hormone-sensitive lipase, and simultaneously inhibit LPL activity. However, LPL regulation is complex and previous studies have described translational regulation of LPL in response to catecholamines because of an RNA-binding protein that interacts with the 3′-untranslated region of LPL mRNA. In this study, we identified several protein components of an LPL RNA binding complex. Using an LPL RNA affinity column, we identified two of …
Regulation Of Lipoprotein Lipase By Protein Kinase Cα In 3t3-F442a Adipocytes, Gouri Ranganathan, Wei Song, Nicholas Dean, Brett Monia, Steven W. Barger, Philip A. Kern
Regulation Of Lipoprotein Lipase By Protein Kinase Cα In 3t3-F442a Adipocytes, Gouri Ranganathan, Wei Song, Nicholas Dean, Brett Monia, Steven W. Barger, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is an important enzyme in adipocyte and lipid metabolism with complex cellular regulation. Previous studies demonstrated an inhibition of LPL activity and synthesis following depletion of protein kinase C (PKC) isoforms with long term treatment of 3T3-F442A adipocytes with 12-O-tetradecanoylphorbol-13-acetate. To identify the specific PKC isoforms involved, we treated cells with antisense oligonucleotides that block expression of specific PKC isoforms. An antisense oligonucleotide to PKCα inhibited LPL activity by 78 ± 8%, whereas antisense oligonucleotides directed against PKCδ or PKCε had no effect on LPL activity. The change in LPL activity was maximal at 72 …
The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern
The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern
Clinical and Translational Science Faculty Publications
Adipose tissue lipoprotein lipase (LPL) activity is decreased in patients with poorly controlled diabetes, and this contributes to the dyslipidemia of diabetes. To study the mechanism of this decrease in LPL, we studied adipose tissue LPL expression in male rats with streptozotocin-induced diabetes. Heparin releasable and extractable LPL activity in the epididymal fat decreased by 75-80% in the diabetic group and treatment of the rats with insulin prior to sacrifice reversed this effect. Northern blot analysis indicated no corresponding change in LPL mRNA levels. However, LPL synthetic rate, measured using [35S]methionine pulse labeling, was decreased by 75% in …
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 …
Lack Of Effect Of Leptin On Glucose Transport, Lipoprotein Lipase, And Insulin Action In Adipose And Muscle Cells, Subramanian Ranganathan, Theodore P. Ciaraldi, Robert R. Henry, Sunder Mudaliar, Philip A. Kern
Lack Of Effect Of Leptin On Glucose Transport, Lipoprotein Lipase, And Insulin Action In Adipose And Muscle Cells, Subramanian Ranganathan, Theodore P. Ciaraldi, Robert R. Henry, Sunder Mudaliar, Philip A. Kern
Clinical and Translational Science Faculty Publications
The effect of leptin on glucose transport, lipogenesis, and lipoprotein lipase activity was studied in cultured rat adipocytes and 3T3-L1 adipocytes. Leptin had no effect on basal and insulin stimulated glucose transport in isolated adipocytes from the rat and the genetically obese mouse. The incorporation of glucose into lipids was also unaffected. Lipoprotein lipase (LPL) activity remained unchanged in response to leptin in these cells, as well as in minced adipose tissue. Leptin also had no effect on both basal and insulin-stimulated glucose transport in cultured rat and human skeletal muscle cells. These studies showed that leptin had no effect …
Potential Role Of Tnfα And Lipoprotein Lipase As Candidate Genes For Obesity, Philip A. Kern
Potential Role Of Tnfα And Lipoprotein Lipase As Candidate Genes For Obesity, Philip A. Kern
Clinical and Translational Science Faculty Publications
To maintain body weight, metabolic efficiency was promoted during evolution; two candidate genes for body weight regulation are lipoprotein lipase (LPL) and tumor necrosis factor-α [TNFα). Human fat cells do not synthesize lipid, but rely on LPL-mediated plasma triglyceride hydrolysis. Adipose LPL is elevated in obesity. Following weight loss, LPL is elevated further, suggesting attempts to maintain lipid stores during fasting and to replenish lipid stores during refeeding. Muscle LPL is regulated inversely to adipose LPL. Thus, an increased adipose/muscle LPL ratio would partition dietary lipid into adipose tissue and would explain some of the variability in weight gain when …
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 …
Tissue-Specific Expression Of Human Lipoprotein Lipase: Effect Of The 3′-Untranslated Region On Translation, Gouri Ranganathan, John M. Ong, Ada Yukht, Mehrnoosh Saghizadeh, Rosa B. Simsolo, Andrea Pauer, Philip A. Kern
Tissue-Specific Expression Of Human Lipoprotein Lipase: Effect Of The 3′-Untranslated Region On Translation, Gouri Ranganathan, John M. Ong, Ada Yukht, Mehrnoosh Saghizadeh, Rosa B. Simsolo, Andrea Pauer, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3′-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA …