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PPARα/γ ragaglitazer eliminates fatty liver and enhances insulin action in fat-fed rats in the absence of hepatomegaly
Citation
Ye, JM and Iglesias, MA and Watson, DG and Ellis, B and Wood, L and Jensen, PB and Sorensen, RV and Larsen, PJ and Cooney, GJ and Wassermann, K and Kraegen, EW, PPARα/γ ragaglitazer eliminates fatty liver and enhances insulin action in fat-fed rats in the absence of hepatomegaly, American Journal of Physiology: Endocrinology and Metabolism, 284, (3) pp. E531-540. ISSN 0193-1849 (2003) [Refereed Article]
Copyright Statement
Copyright 2003 the American Physiological Society
Official URL: http://ajpendo.physiology.org/content/284/3/E549.f...
DOI: doi:10.1152/ajpendo.00299.2002
Abstract
Peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonists lower lipid accumulation in muscle and liver by different mechanisms. We investigated whether benefits could be achieved on insulin sensitivity and lipid metabolism by the dual PPARα/γ agonist ragaglitazar in high fat-fed rats. Ragaglitazar completely eliminated high-fat feeding-induced liver triglyceride accumulation and visceral adiposity, like the PPARα agonist Wy-14643 but without causing hepatomegaly. In contrast, the PPARγ agonist rosiglitazone only slightly lessened liver triglyceride without affecting visceral adiposity. Compared with rosiglitazone or Wy-14643, ragaglitazar showed a much greater effect (79%, P < 0.05) to enhance insulin's suppression of hepatic glucose output. Whereas all three PPAR agonists lowered plasma triglyceride levels and lessened muscle long-chain acyl-CoAs, ragaglitazar and rosiglitazone had greater insulin-sensitizing action in muscle than Wy-14643, associated with a threefold increase in plasma adiponectin levels. There was a significant correlation of lipid content and insulin action in liver and particularly muscle with adiponectin levels (P < 0.01). We conclude that the PPARα/γ agonist ragaglitazar has a therapeutic potential for insulin-resistant states as a PPARγ ligand, with possible involvement of adiponectin. Additionally, it can counteract fatty liver, hepatic insulin resistance, and visceral adiposity generally associated with PPARα activation, but without hepatomegaly.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | peroxisome proliferator-activated receptor subtypes, adipokines, tissue lipids, insulin resistance |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Medical biochemistry and metabolomics |
| Research Field: | Metabolic medicine |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Iglesias, MA (Dr Miguel Iglesias) |
| ID Code: | 80265 |
| Year Published: | 2003 |
| Web of Science® Times Cited: | 128 |
| Deposited By: | Health Sciences A |
| Deposited On: | 2012-10-25 |
| Last Modified: | 2013-06-26 |
| Downloads: | 0 |
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