ICEECE2012 Oral Communications Obesity Basic (6 abstracts)
Development of leptin deficient Lepmkyo/Lepmkyo rat-evidence for its superiority over Lepob/Lepob mouse as a model for human obesity
M. Aizawa-Abe 1, , K. Ebihara 1, , C. Ebihara 1 , T. Kusakabe 1 , D. Aotani 1, , V. Gumbili 1 , T. Mashimo 1 , T. Serikawa 1 & K. Nakao 1
1Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Kyoto University Hospital, Kyoto, Japan.
Introduction: It is critical to consider species differences in translating the findings of obesity-model animals into human pathophysiology. Leptin plays an important role in regulating energy homeostasis. Although much has been learned from genetically obese leptin deficient Lepob/Lepob mice, some flaws were noted in mice as animal models for human diabetes.
Methods: To develop a rat leptin-deficient model, we use N-ethyl-N-nitrosourea (ENU) mutagenesis followed by high-efficient screening system. To compare the effect of thiazolidinediones (TZDs) on fatty liver between mouse and rat, we treated 12-week-old male leptin-deficient mice and rats with pioglitazone or rosiglitazone. Parameters of glucose and lipid metabolism, adiposity and PPARγ gene expression in the liver were examined.
Results: We found a leptin-deficient rat strain, Lepmkyo/Lepmkyo, which had a nonsense mutation (Q92X) within the leptin gene. Lepmkyo/Lepmkyo rats showed morbid obesity, glucose intolerance, hypertriglyceridemia and fatty liver, which are comparable to Lepob/Lepob mice. In a striking contrast, treatments with TZDs disclosed marked deterioration of steatohepatitis in obese Lepob/Lepob mice, while they improved steatohepatitis in obese Lepmkyo/Lepmkyo rats as in obese individual. TZDs differentially regulated hepatic peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression and body fat distribution between Lepob/Lepob mice and Lepmkyo/Lepmkyo rats. The present study demonstrates the superiority of Lepmkyo/Lepmkyo rats over Lepob/Lepob mice as animal models of obesity.
Conclusion: The present study provides an evidence of the superiority of Lepmkyo/Lepmkyo rats over Lepob/Lepob mice as a model for human obesity.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
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Endocrine Abstracts
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