| Multi-tissue, selective PPARγ modulation of insulin sensitivity and metabolic pathways in obese rats. | |
| | |
MedLine Citation:
|
PMID: 20959535 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Peroxisome proliferator-activated receptor-γ (PPARγ) ligands, including the insulin-sensitizing thiazolidinedione drugs, transcriptionally regulate hundreds of genes. Little is known about the relationship between PPARγ ligand-specific modulation of cellular mechanisms and insulin sensitization. We characterized the insulin sensitivity and multitissue gene expression profiles of lean and insulin-resistant, obese Zucker rats untreated or treated with one of four PPARγ ligands (pioglitazone, rosiglitazone, troglitazone, and AG-035029). We analyzed the transcriptional profiles of adipose tissue, skeletal muscle, and liver from the rats and determined whether ligand treatment insulin-sensitizing potency was related to ligand treatment-induced alteration of functional pathways. Ligand treatments improved insulin sensitivity in obese rats to varying degrees. Adipose tissue profiles revealed ligand treatment-selective modulation of inflammatory and branched-chain amino acid (BCAA) metabolic pathways, which correlated with ligand treatment-specific insulin-sensitizing potency. Skeletal muscle profiles showed that obese rats exhibited elevated expression of adipocyte and slow-twitch fiber markers, which further increased after ligand treatment, but the magnitude of the treatment-induced changes was not correlated with insulin sensitization. Although PPARγ ligand treatments heterogeneously improved dysregulated expression of cholesterol and fatty acid biosynthetic pathways in obese rat liver, these alterations were not correlated with ligand insulin-sensitizing potency. PPARγ ligand treatment-specific insulin-sensitizing potency correlated with modulation of adipose tissue inflammatory and BCAA metabolic pathways, suggesting a functional relationship between these pathways and whole body insulin sensitivity. Other PPARγ ligand treatment-induced functional pathway changes were detected in adipose tissue, skeletal muscle, and liver profiles but were not related to degree of insulin sensitization. |
| | |
Authors:
|
Gene Hsiao; Justin Chapman; Jachelle M Ofrecio; Jason Wilkes; Jamie L Resnik; Divya Thapar; Shankar Subramaniam; Dorothy D Sears |
Related Documents
:
|
8412775 - Insulin sensitivity of splanchnic and peripheral adipose tissue in vivo in morbidly obe... 10582555 - Aging changes tissue-specific glucose metabolism in rats. 18596725 - Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by mod... 20558665 - Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. 10998075 - Serum homocysteine is weakly associated with von willebrand factor and soluble vascular... 10600805 - Insulin resistance and glucose transporter expression during the euglycemic hyperinsuli... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-19 |
Journal Detail:
|
Title: American journal of physiology. Endocrinology and metabolism Volume: 300 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-29 Completed Date: 2011-01-31 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
|
Languages: eng Pagination: E164-74 Citation Subset: IM |
Affiliation:
|
Department of Bioengineering, University of California, San Diego, CA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adipose Tissue, White
/
metabolism Amino Acids, Branched-Chain / metabolism Animals Gene Expression Profiling Glucose Clamp Technique Hypoglycemic Agents / pharmacology* Inflammation Mediators / metabolism Insulin Resistance* Ligands Liver / metabolism Macrophages / metabolism Male Muscle, Skeletal / metabolism Obesity / blood, drug therapy, metabolism* Oligonucleotide Array Sequence Analysis Organ Specificity PPAR gamma / agonists*, metabolism* Random Allocation Rats Rats, Zucker |
| Grant Support | |
ID/Acronym/Agency:
|
K01-DK-62025/DK/NIDDK NIH HHS; P01-DK-074868/DK/NIDDK NIH HHS; R01-DK-033651/DK/NIDDK NIH HHS; R33-HL-087375/HL/NHLBI NIH HHS; U54-GM-69338/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amino Acids, Branched-Chain; 0/Hypoglycemic Agents; 0/Inflammation Mediators; 0/Ligands; 0/PPAR gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes.
Next Document: Hormonal regulation of energy-protein homeostasis in hemodialysis patients: an anorexigenic profile ...