Online citations, reference lists, and bibliographies.
← Back to Search

The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase MRNA*

G. Ranganathan, C. Li, P. Kern
Published 2000 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
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 the diabetic adipocytes, and insulin treatment reversed this effect. These results suggested regulation of LPL at the level of translation. Diabetic adipocytes demonstrated no change in the distribution of LPL mRNA associated with polysomes, suggesting no inhibition of translation initiation. Addition of cytoplasmic extracts from control and diabetic adipocytes to a reticulocyte lysate system demonstrated the inhibition of LPL translation in vitro. Using different LPL mRNA transcripts in this in vitro translation assay, we found that the 3′-untranslated region (UTR) of the LPL mRNA was important in controlling translation inhibition by the cytoplasmic extracts. To identify the specific region involved, gel shift analysis was performed. A specific shift in mobility was observed when diabetic cytoplasmic extract was added to a transcript containing nucleotides 1818–2000 of the LPL 3′-UTR. Thus, inhibition of translation is the predominant mechanism for the decreased adipose tissue LPL in this insulin-deficient model of diabetes. Translation inhibition involves the interaction of a cytoplasmic factor, probably an RNA-binding protein, with specific sequences of the LPL 3′-UTR.
This paper references
10.1016/0005-2760(93)90196-G
Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level.
S. Enerbäck (1993)
10.1016/0003-2697(87)90021-2
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
P. Chomczyński (1987)
Regulation of adipose tissue lipoprotein lipase gene expression by thyroid hormone in rats.
B. Saffari (1992)
10.2337/diab.32.6.525
The Response of Plasma Triglyceride, Cholesterol, and Lipoprotein Lipase to Treatment in Non-insulin-dependent Diabetic Subjects Without Familial Hypertriglyceridemia
M. Pfeifer (1983)
10.1074/jbc.274.13.9122
Role of Protein Kinase C in the Translational Regulation of Lipoprotein Lipase in Adipocytes*
G. Ranganathan (1999)
Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue.
R. Simsolo (1992)
10.1172/JCI118301
Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3' untranslated region.
A. Yukht (1995)
10.1152/AJPLEGACY.1971.221.3.850
A simple method to determine fat cell size and number in four mammalian species.
M. di Girolamo (1971)
10.1172/JCI114155
Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue.
J. Ong (1989)
Lipoprotein Lipase (Borensztajn, J., ed
R. H. Eckel (1987)
10.1074/JBC.270.13.7149
Tissue-specific Expression of Human Lipoprotein Lipase
G. Ranganathan (1995)
10.1097/00041433-199704000-00005
The tissue-specific expression of lipoprotein lipase: implications for energy and lipoprotein metabolism.
R. Zechner (1997)
10.1126/SCIENCE.3420405
Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3.
C. Holm (1988)
10.1073/PNAS.85.7.2171
Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs.
E. A. Leibold (1988)
Insulin increases the synthetic rate and messenger RNA level of lipoprotein lipase in isolated rat adipocytes.
J. Ong (1988)
Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels.
C. Semenkovich (1989)
10.1007/BF01236268
Lipoprotein lipase activity of adipose tissue and skeletal muscle in insulin-deficient human diabetes
M. R. Taskinen (2005)
10.1002/BIES.950160804
Unmasking the role of the 3' UTR in the cytoplasmic polyadenylation and translational regulation of maternal mRNAs.
M. Wormington (1994)
10.1016/0378-1119(88)90484-2
Tissue-specific regulation of guinea pig lipoprotein lipase; effects of nutritional state and of tumor necrosis factor on mRNA levels in adipose tissue, heart and liver.
S. Enerbäck (1988)
10.1172/JCI108185
Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.
O. Pykälistö (1975)
Enzyme (Basel)
J B Harford (1990)
Expression of lipoprotein lipase in rat muscle: regulation by feeding and hypothyroidism.
J. Ong (1994)
10.1016/0003-2697(87)90541-0
An enzyme-linked immunoassay for lipoprotein lipase.
J. Goers (1987)
Purification of a specific repressor of ferritin mRNA translation from rabbit liver.
W. Walden (1989)
10.1016/S0014-5793(99)01495-7
Lipoprotein lipase, a key role in atherosclerosis?
J. R. Mead (1999)
The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation.
M. Doolittle (1990)
10.1126/SCIENCE.2343304
Reversal of creatine kinase translational repression by 3' untranslated sequences.
J. Ch'ng (1990)
Translational regulation of lipoprotein lipase by thyroid hormone is via a cytoplasmic repressor that interacts with the 3' untranslated region.
P. Kern (1996)
10.1016/S0378-1119(99)00210-3
Initiation of translation in prokaryotes and eukaryotes.
M. Kozak (1999)
The sequence of cDNA encoding lipoprotein lipase. A member of a lipase gene family.
T. Kirchgessner (1987)
10.1074/jbc.272.4.2515
Translational Regulation of Lipoprotein Lipase by Epinephrine Involves a Trans-acting Binding Protein Interacting with the 3′ Untranslated Region*
G. Ranganathan (1997)
A stable, radioactive substrate emulsion for assay of lipoprotein lipase.
P. Nilsson-ehle (1976)
10.1172/JCI116039
Regulation of lipoprotein lipase in the diabetic rat.
K. Tavangar (1992)
10.1126/SCIENCE.3823907
Human lipoprotein lipase complementary DNA sequence.
K. Wion (1987)
10.1172/JCI111675
Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes.
P. Kern (1985)
10.1002/DMR.5610030208
Lipoprotein lipase in diabetes.
M. R. Taskinen (1987)
10.1073/PNAS.84.8.2277
Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells.
J. Rogers (1987)



This paper is referenced by
Characterization of Hypertriglyceridemia in Obese Diabetic TallyHo/Jng Mice
Jennifer Fortuna (2006)
10.1016/j.atherosclerosis.2007.12.011
Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease.
Q. Chen (2008)
PROTECTIVE PROFILE OF CITRULLUS COLOCYNTHIS ROOT EXTRACTS ON LIPID PROFILE STATUS IN STZ CHALLENGED RATS
Sireesha Kalva (2017)
10.1152/AJPCELL.00117.2003
Control of Na+-K+-ATPase β1-subunit expression: role of 3′-untranslated region
Y. Shao (2004)
10.1074/JBC.M209988200
Translational Regulation of Human Neuronal Nitric-oxide Synthase by an Alternatively Spliced 5′-Untranslated Region Leader Exon*
D. Newton (2003)
10.1007/s00109-002-0384-9
Lipoprotein lipase: structure, function, regulation, and role in disease
J. R. Mead (2002)
Estudi de la lipoproteïna lipasa mitjançant eines proteòmiques. Possible participació de l'òxid nítric en la seva regulació
A. Torrequebrada (2009)
10.4161/rna.27655
Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis
Maria Bouvy-Liivrand (2014)
10.1074/JBC.M405937200
Translational Control of β2-Adrenergic Receptor mRNA by T-cell-restricted Intracellular Antigen-related Protein*
Karthikeyan Kandasamy (2005)
ANTI-HYPERLIPIDEMIC EFFECT OF ETHANOLIC LEAF EXTRACT OF GMELINA ARBOREA IN STREPTOZOTOCIN INDUCED MALE WISTAR ALBINO RATS.
D. Punitha (2012)
10.18805/ijar.v0iOF.4552
Antioxidant potentials of Terminalia catappa leaf extractin Streptozotocin induced diabetes in rats
Natarajan Divya (2016)
10.1097/00041433-200210000-00002
Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism
Karina Preiss-Landl (2002)
10.18452/15196
Identification of the tumour-associated gene S100A14 and analysis of its regulation
A. Piętas (2005)
10.1016/J.CMRP.2014.11.012
Antidiabetic along with antihyperlipidemic and antioxidant activity of aqueous extract of Platycladus orientalis in streptozotocin-induced diabetic rats
A. Dash (2014)
10.1074/JBC.M206917200
Regulation of Lipoprotein Lipase by Protein Kinase Cα in 3T3-F442A Adipocytes*
G. Ranganathan (2002)
Hypolipidemic effect of Aegle marmelos leaf extract in streptozotocin (STZ) induced diabetic male albino rats.
V. Kalpana Devi (2010)
Lipid lowering effect of aqueous extract of flower of Cassia auriculata on streptozotocin (STZ) induced diabetic male albino rats.
Aravind Sivaraj (2010)
10.18805/IJAR.B-3337
Protective effect of Psidium guajava leaf ethanolic extract against streptozotocin-induced diabetes and lipidosis in rats
Ramasamy Manikandan (2017)
10.1016/S1995-7645(10)60209-X
Antidiabetic and anti-lipemic effects of Cassia siamea leaves extract in streptozotocin induced diabetic rats
S. Kumar (2010)
10.7897/2230-8407.088140
MODULATORY EFFECT OF LEUCAS ASPERA ON OXIDATIVE STRESS AND GLUCOSE METABOLISM AGAINST DIABETIC COMPLICATIONS IN EXPERIMENTAL RATS
Sidhra Syed Zameer Ahmed (2017)
10.1186/s12906-016-1093-1
Effect of polysaccharide from Bacillus subtilis sp. on cardiovascular diseases and atherogenic indices in diabetic rats
M. M. Ghoneim (2016)
Assessment of antidiabetic and antioxidant activities of Cassia angustifolia and Feoniculum vulgare in diabetic rats
Jambi (2017)
LIPOPROTEIN LIPASE: FROM GENE TO OBESITY Running Title: LPL and Obesity
H. Wang (2009)
10.1016/J.DIABRES.2004.03.005
Short term effects of L-carnitine on serum lipids in STZ-induced diabetic rats.
H. G. Eskandari (2004)
Human gene array analysis of THP-1 macrophages exposed to lipoprotein hydrolysis products generated by lipoprotein lipase
Narmadaa Thyagarajan (2017)
10.1042/BJ20071559
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)
10.1016/S0003-9861(02)00417-4
Evaluation of thyroid hormone effects on liver P450 reductase translation.
E. Apletalina (2003)
10.1152/ajprenal.00111.2012
Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury.
S. Li (2012)
10.7439/IJPR.V4I3.103
Antidiabetic activity of Randia dumetorum against streptozotocin (STZ) induced diabetics in rats
G. Bai (2014)
10.1016/B978-0-08-057480-6.50020-4
CHAPTER 16 – Vector Design for Transgene Expression
L. Houdebine (2002)
10.1210/JC.2006-1195
Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery of a new risk haplotype.
M. Goodarzi (2007)
10.1152/ajpendo.90892.2008
Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids.
Anannya Banga (2009)
See more
Semantic Scholar Logo Some data provided by SemanticScholar