Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-17
pubmed:abstractText
Nonalcoholic steatohepatitis (NASH) is one of the most frequent causes of abnormal liver dysfunction associated with synthesis and oxidation of fatty acids. Adiponectin receptors (AdipoR1/R2) and insulin receptor substrates (IRS-1/-2) are known as modulators of these fatty acid metabolisms in the liver; however, the regulatory roles of these receptors in the synthesis and oxidation of fatty acids are unclear in the liver of NASH. In this study, we examined the roles of hepatic AdipoR1/R2 and IRS-1/-2 in NASH using an animal model. After feeding a high-fat and high-cholesterol diet to obese fa/fa Zucker rats for 8 weeks, rats showed fatty liver spontaneously with inflammation and fibrosis that are characteristic of NASH. The expression levels of AdipoR1/R2 and IRS-2 were significantly decreased, whereas IRS-1 was significantly increased, in NASH. As a result of the decrease of AdipoR1/R2 expression, the messenger RNA expression levels of genes located downstream of AdipoR1/R2, adenosine monophosphate-activated protein kinase ?1/?2, which inhibits fatty acid synthesis, and peroxisome proliferator-activated receptor ?, which activates fatty acid oxidation, also decreased. Expression level of sterol regulatory element binding protein-1c was found to be elevated, suggesting the up-regulation of IRS-1, and resulted in increased fatty acid synthesis. Furthermore, increase of forkhead box protein A2 expression was observed, which might be associated with the down-regulation of IRS-2, facilitating fatty acid oxidation. Taken together, increased synthesis and oxidation of fatty acids by up- or down-regulation of AdipoR or IRS may contribute to the progression of NASH. Thus, AdipoR and IRS might be crucially important regulators for the synthesis and oxidation of fatty acids in the liver of NASH.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, Dietary, http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adiponectin, http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides, http://linkedlifedata.com/resource/pubmed/chemical/adiponectin receptor 1, rat, http://linkedlifedata.com/resource/pubmed/chemical/adiponectin receptor 2, rat
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1532-8600
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
805-14
pubmed:meshHeading
pubmed-meshheading:20846698-Animals, pubmed-meshheading:20846698-Antioxidants, pubmed-meshheading:20846698-Blood Glucose, pubmed-meshheading:20846698-Cholesterol, Dietary, pubmed-meshheading:20846698-Dietary Fats, pubmed-meshheading:20846698-Fatty Acids, pubmed-meshheading:20846698-Fatty Liver, pubmed-meshheading:20846698-Gene Expression Regulation, pubmed-meshheading:20846698-Insulin Receptor Substrate Proteins, pubmed-meshheading:20846698-Lipid Peroxidation, pubmed-meshheading:20846698-Liver, pubmed-meshheading:20846698-Liver Function Tests, pubmed-meshheading:20846698-Male, pubmed-meshheading:20846698-Microsomes, Liver, pubmed-meshheading:20846698-Mitochondria, Liver, pubmed-meshheading:20846698-Oxidative Stress, pubmed-meshheading:20846698-Peroxisomes, pubmed-meshheading:20846698-Rats, pubmed-meshheading:20846698-Rats, Zucker, pubmed-meshheading:20846698-Receptors, Adiponectin, pubmed-meshheading:20846698-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20846698-Triglycerides
pubmed:year
2011
pubmed:articleTitle
Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model.
pubmed:affiliation
Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252-0880, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't