Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines.
The aim of this study was to determine whether inhibition of resistin by a synthetic antiresistin RNA (oligonucleotide) oligo ameliorates metabolic and histological abnormalities in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) in mice. The antiresistin RNA oligo and a scrambled control oligo (25 mg/kg of body weight) were i.p. injected to HFD mice. Serum metabolic parameters and hepatic enzymes were measured after 4-week treatment. The treatment significantly reduced epididymal fat and attenuated the elevated serum resistin, cholesterol, triglycerides, glucose, and insulin with an improved glucose tolerance test. Antiresistin RNA oligo also normalized serum AST and ALT levels with improved pathohistology of NAFLD. Immunoblotting and qRT-PCR revealed that decreased protein and mRNA expression of resistin in fat and liver tissues of the treated mice were associated with reduction of adipose TNF-α and IL-6 expression and secretion into circulation. mRNA and protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and sterol regulatory element-binding protein-1c (SREBP-1c) were also significantly decreased in the treated mice. Our results suggest that resistin may exacerbate NAFLD in metabolic syndrome through upregulating inflammatory cytokines and hepatic PEPCK and SREBP-1c. Antiresistin RNA oligo ameliorated metabolic abnormalities and histopathology of NAFLD through attenuating proinflammatory cytokines.
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Yi
Y
Tan
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Xing Liang
XL
Jin
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Weiguo
W
Lao
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Jane
0000-0003-1408-5984
J
Kim
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Linda
L
Xiao
School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
Xianqin
0000-0002-8260-2384
X
Qu
D000818:Animals; D059305:Diet, High-Fat; D005786:Gene Expression Regulation / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000096:biosynthesis; D012313:RNA / Q000008:administration & dosage / Q000235:genetics; D052243:Resistin / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D009841:Oligonucleotides; D052243:Resistin; C499623:Retn protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; C000597251:PCK2 protein, human; D019764:Phosphoenolpyruvate Carboxykinase (ATP)