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Effects of combined PPARγ and PPARα agonist therapy on reverse cholesterol transport in the Zucker diabetic fatty rat
Author(s) -
Tanabe J.,
Tamasawa N.,
Yamashita M.,
Matsuki K.,
Murakami H.,
Matsui J.,
Sugimoto K.,
Yasujima M.,
Suda T.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00810.x
Subject(s) - fenofibrate , medicine , abcg1 , endocrinology , pioglitazone , insulin resistance , reverse cholesterol transport , agonist , type 2 diabetes , diabetes mellitus , peroxisome proliferator activated receptor , abca1 , rosiglitazone , cholesterol , receptor , chemistry , lipoprotein , biochemistry , transporter , gene
Aim: We investigated the effects of the combined therapy of PPARγ and PPARα agonists on HDL metabolism, especially concerning reverse cholesterol transport (RCT), using Zucker diabetic fatty rats (ZDF/Crl‐Lepr fa rats) that are the rodent model for type 2 diabetes with obesity, hyperlipidaemia and insulin resistance. Methods: The ZDF rats were divided into four medicated groups as follows: pioglitazone as a PPARγ agonist (5 mg/kg/day; P group, n = 6), fenofibrate as a PPARα agonist (30 mg/kg/day; F group, n = 6), both these medications (P + F group, n = 6) and no treatment (UNT group, n = 6). Non‐diabetic rats (ZDF/GmiCrl‐lean, CON group, n = 6) served as controls. We evaluated HDL particle size and messenger RNA (mRNA) levels of the following factors: liver X receptor α (L × R α), ATP‐binding cassette A1 (ABCA1) and ABCG1 which are regulated by PPARs and are related to early stage RCT. Results: The significant increase in HDL particle size was demonstrated in rats of the F and P + F groups, although changes in plasma HDL‐cholesterol levels were not significant. In accordance with this finding, mRNA levels of ABCG1 in the liver increased significantly. Conclusions: These findings suggest the efficacy of combined therapy with PPARγ and PPARα in improving lipid metabolism, partly through the enhanced RCT, and insulin resistance in type 2 diabetes mellitus.