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Experimental Diabetes Research
Volume 2012, Article ID 789730, 8 pages
Research Article

Inhibition of Aldose Reductase Activates Hepatic Peroxisome Proliferator-Activated Receptor-α and Ameliorates Hepatosteatosis in Diabetic db/db Mice

1State Key Laboratory for Stress Cellular Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiamen 361005, China
2School of Life Sciences, and Fujian Key Laboratory of Preventive Veterinary Medicine and Biotechnology, Longyan University, Longyan 364000, China
3School of Nursing, The Third Military Medical University, Chongqing 400038, China
4Xiamen University Laboratory Animal Center, Xiamen University, Xiamen 361005, China

Received 6 June 2011; Revised 23 August 2011; Accepted 29 August 2011

Academic Editor: Konstantinos Kantartzis

Copyright © 2012 Longxin Qiu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPARα, leading to its activation and significant reductions in serum lipid levels. Herein, we report that inhibition of AR by zopolrestat or by a short-hairpin RNA (shRNA) against AR caused a significant reduction in serum and hepatic triglycerides levels in 10-week old diabetic db/db mice. Meanwhile, hyperglycemia-induced phosphorylation of hepatic ERK1/2 and PPARα was significantly attenuated in db/db mice treated with zopolrestat or AR shRNA. Further, in comparison with the untreated db/db mice, the hepatic mRNA expression of Aco and ApoA5, two target genes for PPARα, was increased by 93% (P<0.05) and 73% (P<0.05) in zopolrestat-treated mice, respectively. Together, these data indicate that inhibition of AR might lead to significant amelioration in hyperglycemia-induced dyslipidemia and nonalcoholic fatty liver disease.