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Horm Metab Res 2011; 43(09): 631-635
DOI: 10.1055/s-0031-1280781
Animals
Georg Thieme Verlag KG Stuttgart · NewYork

Pharmacological Activation of Peroxisome Proliferator-activated Receptor δ Improves Insulin Resistance and Hepatic Steatosis in High Fat Diet-induced Diabetic Mice

H.-T. Wu   *
1   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
,
C.-T. Chen   *
2   Department of Pediatrics and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan, R.O.C.
,
K.-C. Cheng
3   Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Japan
,
Y.-X. Li
3   Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Japan
,
C.-H. Yeh
4   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan, R.O.C.
,
J.-T. Cheng
1   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
2   Department of Pediatrics and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan, R.O.C.
4   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan, R.O.C.
› Author Affiliations
Further Information

Publication History

received 23 April 2011

accepted 23 May 2011

Publication Date:
01 July 2011 (online)

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Abstract

The mechanisms regarding hepatic steatosis related to hepatic insulin resistance have been well documented. However, the agents for treatment of hepatic steatosis and insulin resistance remain poorly developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that are responsible for the regulation of glucose and/or lipid metabolism. There are 3 distinct isoforms of PPARs family: PPARα, PPARγ, and PPARδ. Both PPARα and PPARγ agonists are widely used in clinic for the treatment of hyperlipidemia and hyperglycemia. However, the therapeutic efficacy of PPARδ agonists for diabetic disorders remains obscure. In the present study, we used L-165041 as PPARδ agonist to treat the high fat diet (HFD) fed mice. Administration of L-165041 improved the hepatic steatosis and increased the insulin sensitivity in HFD-mice. In addition to the histological identification of hepatic steatosis, the improvement of insulin sensitivity was characterized by the enhanced insulin signals and the increase of hepatic glycogen content. This is the first report showing that pharmacological activation of PPARδ improves insulin resistance in diet-induced diabetic mice. Thus, we suggest that pharmacological activation of PPARδ may be a new strategy for the treatment of diabetic patients with hepatic steatosis.

Key words

diabetes - hepatic steatosis - high fat diet - insulin resistance - peroxisome proliferator-activated receptor δ
*

* These authors contributed equally to this study.


 

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