Document Detail


Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity.
MedLine Citation:
PMID:  18640384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin resistance is a key pathophysiological feature of metabolic syndrome. However, the initial events triggering the development of insulin resistance and its causal relations with dysregulation of glucose and fatty acids metabolism remain unclear. We investigated biological pathways that have the potential to induce insulin resistance in mice fed a high-fat diet (HFD). We demonstrate that the pathways for reactive oxygen species (ROS) production and oxidative stress are coordinately up-regulated in both the liver and adipose tissue of mice fed an HFD before the onset of insulin resistance through discrete mechanism. In the liver, an HFD up-regulated genes involved in sterol regulatory element binding protein 1c-related fatty acid synthesis and peroxisome proliferator-activated receptor alpha-related fatty acid oxidation. In the adipose tissue, however, the HFD down-regulated genes involved in fatty acid synthesis and up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Furthermore, increased ROS production preceded the elevation of tumor necrosis factor-alpha and free fatty acids in the plasma and liver. The ROS may be an initial key event triggering HFD-induced insulin resistance.
Authors:
Naoto Matsuzawa-Nagata; Toshinari Takamura; Hitoshi Ando; Seiji Nakamura; Seiichiro Kurita; Hirofumi Misu; Tsuguhito Ota; Masayoshi Yokoyama; Masao Honda; Ken-ichi Miyamoto; Shuichi Kaneko
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  57     ISSN:  1532-8600     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-09-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1071-7     Citation Subset:  IM    
Affiliation:
Department of Medicinal Informatics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism
Animals
Blood Glucose / metabolism
Body Weight / physiology
Dietary Fats / administration & dosage*
Glucose Tolerance Test
Insulin / blood
Insulin Resistance / physiology*
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Obesity / metabolism*
Oxidative Stress / physiology*
RNA, Messenger / biosynthesis,  genetics
Reactive Oxygen Species / metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Dietary Fats; 0/RNA, Messenger; 0/Reactive Oxygen Species; 11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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