Suppression of retinol-binding protein 4 with RNA oligonucleotide prevents high-fat diet-induced metabolic syndrome and non-alcoholic fatty liver disease in mice

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dc.contributor.author Tan, Y
dc.contributor.author Sun, L-Q
dc.contributor.author Kamal, MA
dc.contributor.author Wang, X
dc.contributor.author Seale, JP
dc.contributor.author Qu, X
dc.date.accessioned 2012-10-12T03:33:32Z
dc.date.issued 2011-12
dc.identifier.citation Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 2011, 1811 (12), pp. 1045 - 1053
dc.identifier.issn 1388-1981
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/18193
dc.description.abstract Conflicting data have been reported regarding the role of retinol-binding protein (RBP4) in insulin resistance, obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this study, we used pharmacological methods to investigate the role of RBP4. RNA oligonucleotide against RBP4 (anti-RBP4 oligo) was transfected into 3T3-L1 adipocytes. RT-PCR analysis showed that RBP4 mRNA expression decreased by 55% (p < 0.01) compared with control cells. Validated RNA oligo was used in an in vivo study with high fat diet (HFD) fed - mice. 14 weeks of HFD feeding increased RBP4 expression (associated with elevated serum levels measured with immunoblotting and ELISA) by 56% in adipose tissue (p < 0.05) and 68% in the liver (p < 0.01). Adipose RBP4 levels were significantly reduced after 4 weeks treatment with anti-RBP4 oligo (25 mg/kg, p < 0.01) and rosiglitazone (RSG, 10 mg/kg, p < 0.05) compared with scrambled RNA oligo (25 mg/kg) treated mice. Only anti-RBP4 oligo significantly inhibited RBP4 protein (p < 0.01) and mRNA expression (p < 0.01) in the liver and reduced serum RBP4 levels. Anti-RBP4 oligo and RSG showed comparable effects on impaired glucose tolerance, hyperinsulinaemia and hyperglycaemia. Anti-RBP4 oligo significantly enhanced adipose-GLUT4 expression (p < 0.01) but did not increase muscle-GLUT4. Both RSG and anti-RBP4 oligo significantly reduced hepatic phosphoenolpyruvate carboxykinase expression (both p < 0.05). Histological analysis revealed that anti-RBP4 oligo ameliorated hepatic steatosis and reduced lipid droplets associated with normalized liver function. Histological and pharmacological results of this study indicate that RBP4 is not only an adipocytokine, but also a hepatic cytokine leading to metabolic syndrome, NAFLD and type 2 diabetes. © 2011 Published by Elsevier B.V. All rights reserved.
dc.language eng
dc.relation.isbasedon 10.1016/j.bbalip.2011.09.011
dc.subject Anti-RBP4 RNA oligonucleotide, High fat diet fed mice, Metabolic syndrome, Non-alcoholic fatty liver disease, RBP4 inhibition, Retinol-binding protein 4, Animals, Mice, Inbred C57BL, Mice, Adipose Tissue, Liver, 3T3-L1 Cells, Fatty Liver, Diabetes Mellitus, Type 2, Insulin Resistance, Metabolic Syndrome X, Thiazolidinediones, Insulin, Oligonucleotides, Antisense, Blood Glucose, Transfection, Retinol-Binding Proteins, Plasma, Adipocytes, Diet, High-Fat, Male, Glucose Transporter Type 4, 3T3-L1 Cells, Adipocytes, Adipose Tissue, Animals, Blood Glucose, Diabetes Mellitus, Type 2, Diet, High-Fat, Fatty Liver, Glucose Transporter Type 4, Insulin, Insulin Resistance, Liver, Male, Metabolic Syndrome X, Mice, Mice, Inbred C57BL, Oligonucleotides, Antisense, Retinol-Binding Proteins, Plasma, Thiazolidinediones, Transfection, Anti-RBP4 RNA oligonucleotide, High fat diet fed mice, Metabolic syndrome, Non-alcoholic fatty liver disease, RBP4 inhibition, Retinol-binding protein 4
dc.subject Anti-RBP4 RNA oligonucleotide; High fat diet fed mice; Metabolic syndrome; Non-alcoholic fatty liver disease; RBP4 inhibition; Retinol-binding protein 4; Animals; Mice, Inbred C57BL; Mice; Adipose Tissue; Liver; 3T3-L1 Cells; Fatty Liver; Diabetes Mellitus, Type 2; Insulin Resistance; Metabolic Syndrome X; Thiazolidinediones; Insulin; Oligonucleotides, Antisense; Blood Glucose; Transfection; Retinol-Binding Proteins, Plasma; Adipocytes; Diet, High-Fat; Male; Glucose Transporter Type 4; 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Fatty Liver; Glucose Transporter Type 4; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome X; Mice; Mice, Inbred C57BL; Oligonucleotides, Antisense; Retinol-Binding Proteins, Plasma; Thiazolidinediones; Transfection; Anti-RBP4 RNA oligonucleotide; High fat diet fed mice; Metabolic syndrome; Non-alcoholic fatty liver disease; RBP4 inhibition; Retinol-binding protein 4
dc.title Suppression of retinol-binding protein 4 with RNA oligonucleotide prevents high-fat diet-induced metabolic syndrome and non-alcoholic fatty liver disease in mice
dc.type Journal Article
dc.parent Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
dc.journal.volume 12
dc.journal.volume 1811
dc.journal.number 12 en_US
dc.publocation Netherlands en_US
dc.identifier.startpage 1045 en_US
dc.identifier.endpage 1053 en_US
dc.cauo.name SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 0601 Biochemistry and Cell Biology
dc.personcode 996685 en_US
dc.personcode 104335 en_US
dc.personcode 101972 en_US
dc.personcode 0000049524 en_US
dc.personcode 0000075520 en_US
dc.personcode 980838 en_US
dc.percentage 100 en_US
dc.classification.name Biochemistry and Cell Biology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords Anti-RBP4 RNA oligonucleotide; High fat diet fed mice; Metabolic syndrome; Non-alcoholic fatty liver disease; RBP4 inhibition; Retinol-binding protein 4 en_US
dc.description.keywords Liver
dc.description.keywords Adipose Tissue
dc.description.keywords 3T3-L1 Cells
dc.description.keywords Adipocytes
dc.description.keywords Animals
dc.description.keywords Mice, Inbred C57BL
dc.description.keywords Mice
dc.description.keywords Fatty Liver
dc.description.keywords Diabetes Mellitus, Type 2
dc.description.keywords Insulin Resistance
dc.description.keywords Metabolic Syndrome X
dc.description.keywords Thiazolidinediones
dc.description.keywords Insulin
dc.description.keywords Blood Glucose
dc.description.keywords Oligonucleotides, Antisense
dc.description.keywords Transfection
dc.description.keywords Male
dc.description.keywords Glucose Transporter Type 4
dc.description.keywords Retinol-Binding Proteins, Plasma
dc.description.keywords Diet, High-Fat
dc.description.keywords Animals
dc.description.keywords Mice, Inbred C57BL
dc.description.keywords Mice
dc.description.keywords Adipose Tissue
dc.description.keywords Liver
dc.description.keywords 3T3-L1 Cells
dc.description.keywords Fatty Liver
dc.description.keywords Diabetes Mellitus, Type 2
dc.description.keywords Insulin Resistance
dc.description.keywords Metabolic Syndrome X
dc.description.keywords Thiazolidinediones
dc.description.keywords Insulin
dc.description.keywords Oligonucleotides, Antisense
dc.description.keywords Blood Glucose
dc.description.keywords Transfection
dc.description.keywords Retinol-Binding Proteins, Plasma
dc.description.keywords Adipocytes
dc.description.keywords Diet, High-Fat
dc.description.keywords Male
dc.description.keywords Glucose Transporter Type 4
dc.description.keywords Anti-RBP4 RNA oligonucleotide
dc.description.keywords High fat diet fed mice
dc.description.keywords Metabolic syndrome
dc.description.keywords Non-alcoholic fatty liver disease
dc.description.keywords RBP4 inhibition
dc.description.keywords Retinol-binding protein 4
dc.description.keywords Anti-RBP4 RNA oligonucleotide
dc.description.keywords High fat diet fed mice
dc.description.keywords Metabolic syndrome
dc.description.keywords Non-alcoholic fatty liver disease
dc.description.keywords RBP4 inhibition
dc.description.keywords Retinol-binding protein 4
dc.description.keywords Anti-RBP4 RNA oligonucleotide
dc.description.keywords High fat diet fed mice
dc.description.keywords Metabolic syndrome
dc.description.keywords Non-alcoholic fatty liver disease
dc.description.keywords RBP4 inhibition
dc.description.keywords Retinol-binding protein 4
dc.staffid en_US
dc.staffid 980838 en_US
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies


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