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Thiazolidinediones Inhibit Lipoprotein Lipase Activity In Adipocytes*

S. Ranganathan, P. Kern
Published 1998 · Medicine, Biology

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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 undifferentiated 3T3-F442A and 3T3-L1 cells and had no effect on mRNA expression or synthesis of lipoprotein lipase in differentiated cells. Western blot analysis showed that these drugs did not affect the mass of the enzyme protein. Lipoprotein lipase activity in cultured Chinese hamster ovary cells was not inhibited by troglitazone. Glucose transport, biosynthesis of lipids from glucose or the biosynthesis of proteins were unaffected by thiazolidinediones in differentiated cells, whereas glucose transport and lipid biosynthesis were increased when these drugs were added during differentiation. These results show that troglitazone and BRL 49653 have a specific, post-translational inhibitory effect on lipoprotein lipase in adipocytes, yet they promote lipid accumulation and differentiation in preadipocytes.
This paper references
Troglitazone Inhibits Fatty Acid Oxidation and Esterification, and Gluconeogenesis in Isolated Hepatocytes from Starved Rats
J. Fulgencio (1996)
Insulin increases the synthetic rate and messenger RNA level of lipoprotein lipase in isolated rat adipocytes.
J. Ong (1988)
Maturation of lipoprotein lipase. Expression of full catalytic activity requires glucose trimming but not translocation to the cis-Golgi compartment.
O. Ben-Zeev (1992)
Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue.
R. Simsolo (1992)
Biological Actions of Insulin Are Differentially Regulated by Glucose and Insulin in Primary Cultured Adipocytes: Chronic Ability to Increase Glycogen Synthase Activity
F. Lima (1994)
Comparison of free fatty acid and glyceride--fatty acid uptake by human adipose tissue.
J. Wilson (1973)
Adipocyte differentiation: a transcriptional regulatory cascade.
R. Brun (1996)
Troglitazone action is independent of adipose tissue.
C. Burant (1997)
Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia.
R. Law (1996)
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
P. Chomczyński (1987)
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
P. Tontonoz (1994)
A.-M Lefebvre (1997)
The Organization, Promoter Analysis, and Expression of the Human PPARγ Gene*
L. Fajas (1997)
Adipogenesis and Obesity: Rounding Out the Big Picture
B. Spiegelman (1996)
Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels.
C. Semenkovich (1989)
Localization of a pioglitazone response element in the adipocyte fatty acid-binding protein gene.
P. K. Harris (1994)
An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ) (*)
J. Lehmann (1995)
The origin and glyceride distribution of fatty acids in rat adipose tissue.
C. Hollenberg (1966)
Synthesis and secretion of lipoprotein lipase in 3T3-L1 adipocytes. Demonstration of inactive forms of lipase in cells.
T. Olivecrona (1987)
PPARalpha and PPARgamma activators direct a distinct tissue‐specific transcriptional response via a PPRE in the lipoprotein lipase gene.
K. Schoonjans (1996)
Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue.
J. Ong (1989)
Actions of Novel Antidiabetic Agent Englitazone in Hyperglycemic Hyperinsulinemic ob/ob Mice
R. W. Stevenson (1990)
Effects of troglitazone on in vitro oxidation of LDL and HDL induced by copper ions and endothelial cells
L. Cominacini (1997)
Enhancement of adipocyte differentiation by an insulin-sensitizing agent.
R. Kletzien (1992)
Hexose transport stimulation and membrane redistribution of glucose transporter isoforms in response to cholera toxin, dibutyryl cyclic AMP, and insulin in 3T3-L1 adipocytes.
B. Clancy (1990)
Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3' untranslated region.
A. Yukht (1995)
Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level.
S. Enerbäck (1993)
Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes.
P. Kern (1985)
The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation.
M. Doolittle (1990)
Regulation of Lipoprotein Metabolism by Thiazolidinediones Occurs through a Distinct but Complementary Mechanism Relative to Fibrates
Anne-Marie Lefebvre (1997)
The Response of Plasma Triglyceride, Cholesterol, and Lipoprotein Lipase to Treatment in Non-insulin-dependent Diabetic Subjects Without Familial Hypertriglyceridemia
M. Pfeifer (1983)
Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival.
A. Chawla (1994)
Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides.
P. Belfrage (1969)
George Lyman Duff Memorial Lecture. Atherogenesis in diabetes.
E. Bierman (1992)
Antidiabetic agent pioglitazone enhances adipocyte differentiation of 3T3-F442A cells.
T. Sandouk (1993)
Fatty acid synthesis in human adipose tissue.
E. Shrago (1969)
Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.
O. Pykälistö (1975)
Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes
A. Saltiel (1996)
A stable, radioactive substrate emulsion for assay of lipoprotein lipase.
P. Nilsson-ehle (1976)
Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.
H. Keller (1993)

This paper is referenced by
Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution
L. Pickavance (1999)
Peroxisome proliferator-activated receptors in atherosclerosis.
J. Medh (1999)
Rôle des Peroxisome Proliferator-Activated Receptors (PPAR) dans le métabolisme lipidique
Florian Laracine (2009)
Regulation of lipoprotein lipase gene expression by insulin and troglitazone in rainbow trout (Oncorhynchus mykiss) adipocyte cells in culture.
L. Bouraoui (2012)
Lipoprotein lipase, a key role in atherosclerosis?
J. R. Mead (1999)
Transgenic Mice Expressing Lipoprotein Lipase in Adipose Tissue
Lori L Hensley (2003)
Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes.
Angela M. Bodles (2006)
Direct thiazolidinedione action on isolated rat skeletal muscle fuel handling is independent of peroxisome proliferator-activated receptor-gamma-mediated changes in gene expression.
B. Brunmair (2001)
A single element in the phosphoenolpyruvate carboxykinase gene mediates thiazolidinedione action specifically in adipocytes.
M. Glorian (2001)
Receptor-Independent Metabolic Effects of Thiazolidinediones in Astrocytes
Candan A Akar (2010)
Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury.
S. Li (2012)
Troglitazone prevents and reverses dexamethasone induced insulin resistance on glycogen synthesis in 3T3 adipocytes
K. L. Anil Kumar (2000)
Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
S. Kersten (2008)
The stimulation of tumor necrosis factor and inhibition of glucose transport and lipoprotein lipase in adipose cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
P. Kern (2002)
Therapeutic interventions for lipid-induced insulin resistance in skeletal muscle: mechanisms of action
S. Lessard (2006)
The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes
G. Tan (2004)
Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key?
D. Feinstein (2005)
Expression and regulation of mitogen-activated protein kinase (MAPK) phosphatases (MKPs) in adipogenesis
S. Bjørklund (2006)
Regulation of Lipoprotein Lipase by Protein Kinase Cα in 3T3-F442A Adipocytes*
G. Ranganathan (2002)
Troglitazone: the discovery and development of a novel therapy for the treatment of Type 2 diabetes mellitus.
J. Parker (2002)
Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein lipase.
G. Ranganathan (2005)
Translational regulation of lipoprotein lipase in adipocytes: depletion of cellular protein kinase Calpha activates binding of the C subunit of protein kinase A to the 3'-untranslated region of the lipoprotein lipase mRNA.
R. Unal (2008)
Peroxisome proliferator-activated receptor-α ligands inhibit cardiac lipoprotein lipase activity
R. Carroll (2001)
Troglitazone inhibits expression of the phosphoenolpyruvate carboxykinase gene by an insulin-independent mechanism.
G. Davies (1999)
The Clinical Effectiveness and Cost Effectiveness of Rosiglitazone for Type 2 Diabetes Mellitus
J. Lord (2000)
Ameliorated Hepatic Insulin Resistance Is Associated with Normalization of Microsomal Triglyceride Transfer Protein Expression and Reduction in Very Low Density Lipoprotein Assembly and Secretion in the Fructose-fed Hamster*
A. Carpentier (2002)
Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes.
J. Rieusset (1999)
Current trends and new approaches in the management of diabetes mellitus.
P. Kao (2000)
New mechanism-based anticancer drugs that act as orphan nuclear receptor agonists
Sudhakar Chintharlapalli (2007)
Enhancement of the Aquaporin Adipose Gene Expression by a Peroxisome Proliferator-activated Receptor γ*
K. Kishida (2001)
The HIV protease inhibitor saquinavir impairs lipid metabolism and glucose transport in cultured adipocytes.
S. Ranganathan (2002)
Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation.
H. Kondo (2002)
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