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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2008-5-2
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pubmed:abstractText |
Agonism of peroxisome proliferator-activated receptor (PPAR) alpha, a key regulator of lipid metabolism, leads to amelioration of lipid abnormalities in dyslipidemic patients. However, whether PPARalpha agonism is an effective form of therapy for obesity-related insulin resistance associated with lipid abnormalities is unclear. The present study investigated the effects of a potent and subtype-selective PPARalpha agonist, KRP-101, in a nonrodent insulin-resistant animal model under pair-fed conditions. Beagle dogs were fed a high-fat diet for 24 wk to induce insulin resistance. During the final 12 wk, 0.03 mg x kg(-1) x day(-1) KRP-101 (n = 5) or vehicle (n = 5) was administered orally once a day. KRP-101 administration resulted in a significantly lower weight of overall visceral fat, which is associated with increased adiponectin and decreased leptin in serum. KRP-101 administration improved hyperglycemia and hyperinsulinemia as well as dyslipidemia in dogs fed a high-fat diet. Oral glucose tolerance test showed that KRP-101 administration improved glucose intolerance. The KRP-101 group showed a markedly lower hepatic triglyceride concentration. Lipid oxidation was increased in the liver and skeletal muscles of the KRP-101 group. These findings in the dog model suggest that the use of potent and subtype-selective PPARalpha agonists as a potentially relevant therapeutic approach to treat human insulin resistance associated with visceral obesity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adiponectin,
http://linkedlifedata.com/resource/pubmed/chemical/Butyric Acids,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Fenofibrate,
http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR delta,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/fenofibric acid
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0193-1849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E833-40
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18212024-Adiponectin,
pubmed-meshheading:18212024-Adipose Tissue,
pubmed-meshheading:18212024-Animals,
pubmed-meshheading:18212024-Butyric Acids,
pubmed-meshheading:18212024-DNA, Complementary,
pubmed-meshheading:18212024-Dietary Fats,
pubmed-meshheading:18212024-Dogs,
pubmed-meshheading:18212024-Dose-Response Relationship, Drug,
pubmed-meshheading:18212024-Fatty Acids,
pubmed-meshheading:18212024-Fenofibrate,
pubmed-meshheading:18212024-Genes, Reporter,
pubmed-meshheading:18212024-Humans,
pubmed-meshheading:18212024-Hypolipidemic Agents,
pubmed-meshheading:18212024-Insulin Resistance,
pubmed-meshheading:18212024-Lipids,
pubmed-meshheading:18212024-Liver,
pubmed-meshheading:18212024-Luciferases,
pubmed-meshheading:18212024-Male,
pubmed-meshheading:18212024-Obesity,
pubmed-meshheading:18212024-Oxidation-Reduction,
pubmed-meshheading:18212024-PPAR alpha,
pubmed-meshheading:18212024-PPAR delta,
pubmed-meshheading:18212024-PPAR gamma,
pubmed-meshheading:18212024-Rats,
pubmed-meshheading:18212024-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18212024-Transcriptional Activation
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pubmed:year |
2008
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pubmed:articleTitle |
A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet.
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pubmed:affiliation |
Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
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pubmed:publicationType |
Journal Article
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