Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats
Background: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we qu...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2020-04-01
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| Series: | Dubai Medical Journal |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/506899 |
| _version_ | 1819011823555313664 |
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| author | Mahmoud M. Farag Ehab H. Ashour Wessam F. El-Hadidy |
| author_facet | Mahmoud M. Farag Ehab H. Ashour Wessam F. El-Hadidy |
| author_sort | Mahmoud M. Farag |
| collection | DOAJ |
| description | Background: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we questioned whether fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR)-α agonist, and pioglitazone (PG), a PPAR-γ agonist, might be effective in ameliorating the metabolic syndrome in a rat model. Materials and Methods: The metabolic syndrome was induced by feeding rats a high-Fr (60%) diet for 10 weeks. The rats were divided into 5 groups: control group, fed a normal rat chow; Fr + vehicle group; Fr + FF group; Fr + PG group; and Fr + (FF + PG) group (treated with both drugs). Drug or vehicle treatment was given daily for 6 weeks (from weeks 5 to 10). Thereafter, blood and liver samples were obtained for biochemical studies. Results: Rats fed a high-Fr diet developed hyperglycemia, hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypercholesterolemia, and had increased serum alanine aminotransferase, hepatic tumor necrosis factor-α, and malondialdehyde levels but decreases in both glutathione content and superoxide dismutase activity. Rat treatment with FF and/or PG attenuated these alterations. The improvement was greater with the combined treatment than with either drug alone, and normalization of insulin sensitivity was observed only in rats treated with the combination therapy. Conclusion: Acting on the 2 main PPAR subfamilies, the combination of FF and PG provides a more efficacious therapy for modulating the changes in serum insulin, uric acid, and lipids, as well as the accompanying hepatic inflammation and oxidative stress that characterize the Fr-induced metabolic syndrome. |
| first_indexed | 2024-12-21T01:34:17Z |
| format | Article |
| id | doaj.art-85e33a6ded5a4e52add68d6ed581a488 |
| institution | Directory Open Access Journal |
| issn | 2571-726X |
| language | English |
| last_indexed | 2024-12-21T01:34:17Z |
| publishDate | 2020-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Dubai Medical Journal |
| spelling | doaj.art-85e33a6ded5a4e52add68d6ed581a4882022-12-21T19:20:18ZengKarger PublishersDubai Medical Journal2571-726X2020-04-0111110.1159/000506899506899Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in RatsMahmoud M. FaragEhab H. AshourWessam F. El-HadidyBackground: The use of high-fructose (Fr) corn sweeteners and sucrose in manufactured food has markedly increased recently. This excessive Fr intake has been proposed in the etiology of the metabolic syndrome, which shows an increasing prevalence throughout the world. Objective: In this study, we questioned whether fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR)-α agonist, and pioglitazone (PG), a PPAR-γ agonist, might be effective in ameliorating the metabolic syndrome in a rat model. Materials and Methods: The metabolic syndrome was induced by feeding rats a high-Fr (60%) diet for 10 weeks. The rats were divided into 5 groups: control group, fed a normal rat chow; Fr + vehicle group; Fr + FF group; Fr + PG group; and Fr + (FF + PG) group (treated with both drugs). Drug or vehicle treatment was given daily for 6 weeks (from weeks 5 to 10). Thereafter, blood and liver samples were obtained for biochemical studies. Results: Rats fed a high-Fr diet developed hyperglycemia, hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypercholesterolemia, and had increased serum alanine aminotransferase, hepatic tumor necrosis factor-α, and malondialdehyde levels but decreases in both glutathione content and superoxide dismutase activity. Rat treatment with FF and/or PG attenuated these alterations. The improvement was greater with the combined treatment than with either drug alone, and normalization of insulin sensitivity was observed only in rats treated with the combination therapy. Conclusion: Acting on the 2 main PPAR subfamilies, the combination of FF and PG provides a more efficacious therapy for modulating the changes in serum insulin, uric acid, and lipids, as well as the accompanying hepatic inflammation and oxidative stress that characterize the Fr-induced metabolic syndrome.https://www.karger.com/Article/FullText/506899fenofibratehigh fructose dietinsulin resistancemetabolic syndromepioglitazoneuric acid |
| spellingShingle | Mahmoud M. Farag Ehab H. Ashour Wessam F. El-Hadidy Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats Dubai Medical Journal fenofibrate high fructose diet insulin resistance metabolic syndrome pioglitazone uric acid |
| title | Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats |
| title_full | Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats |
| title_fullStr | Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats |
| title_full_unstemmed | Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats |
| title_short | Amelioration of High Fructose Diet-Induced Insulin Resistance, Hyperuricemia, and Liver Oxidative Stress by Combined Use of Selective Agonists of PPAR-α and PPAR-γ in Rats |
| title_sort | amelioration of high fructose diet induced insulin resistance hyperuricemia and liver oxidative stress by combined use of selective agonists of ppar α and ppar γ in rats |
| topic | fenofibrate high fructose diet insulin resistance metabolic syndrome pioglitazone uric acid |
| url | https://www.karger.com/Article/FullText/506899 |
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