| Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats: a possible mechanism to prevent high-fat-induced insulin resistance. | |
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MedLine Citation:
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PMID: 21034554 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: As an agonist of peroxisome proliferator-activated receptor-gamma (PPARγ), rosiglitazone can prevent acute fatty acid-induced insulin resistance in rats, however, the precise mechanisms by which rosiglitazone alleviates insulin resistance induced by high-fat diet need to be further investigated. METHODS: Wistar rats aged 23-24 weeks were divided into three groups: (1) aged control group (OC), (2) high-fat diet (HF) group and (3) high-fat diet plus rosiglitazone maleate tablets (HF + Rosi) treatment group (n = 20 in each group). Insulin sensitivity was evaluated by conscious hyperinsulinemic-euglycemic clamp technique. mRNA levels of fatty acid translocase (FAT/CD36), AMP-activated protein kinase α1 (AMPKα1), AMPKα2 and acetyl CoA carboxylase (ACC) of rat skeletal muscle were determined using real-time PCR, while muscle carnitine palmitoyltransferase-1 (CPT-1β) was determined using semi-quantitative PCR. Protein expression levels of FAT/CD36, AMPK phosphorylation (reflecting AMPK activity), P-ACC (inversely related with ACC activity) and muscle CPT-1M in rat skeletal muscles were measured using Western blotting. RESULTS: Aged rats fed by diet rich in fat for more than 8 weeks led to significant increases of plasma lipids, skeletal muscle intramuscular triglyceride and long-chain fatty acyl-CoA (LCACoA) compared to aged rats fed by normal chow diet (OC) (P < 0.05), which might correlate with the lower (reduced by 42.4%) whole body insulin sensitivity in HF rats. FAT/CD36 protein concentrations and mRNA levels increased in untreated HF aged rats (P < 0.01) and high-fat diet induced a significant decrease in P-AMPK, P-ACC, CPT-1M protein concentrations and AMPKα2 and CPT-1β mRNA levels in rat skeletal muscles (P < 0.05). No change in AMPKα1 mRNA levels was observed in the HF group. CONCLUSION: High-fat diet in aged rats results in a lipid accumulation and subsequent insulin resistance, while rosiglitazone can alleviate the insulin resistance by reducing fatty acid uptake as well as enhancing lipometabolism. |
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Authors:
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Guang-yao Song; Yu Gao; Chao Wang; Shu-guo Hu; Jing Wang; Dong-ming Qu; Hui-juan Ma |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chinese medical journal Volume: 123 ISSN: 0366-6999 ISO Abbreviation: Chin. Med. J. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-11-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7513795 Medline TA: Chin Med J (Engl) Country: China |
Other Details:
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Languages: eng Pagination: 2384-91 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, General Hospital of Hebei Province, Shijiazhuang, Hebei 050051, China. sguangyao@sohu.com |
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