Elucidation of molecular mechanism of leptin resistance, using transgenic mice over-expressing leptin

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Clinical trial of recombinant leptin for the treatment of obesity is on going in the United States. However, it has been reported that the efficacy of leptin treatment by the peripheral administration is quite limited, probably because the most obese people may be in a leptin-resistant state. Recently, we developed transgenic mice over-expressing leptin, which have high sensitivity to leptin, despite an increased concentration of serum leptin comparable to that in obese people. In this project, we explored the pathogenic mechanism of leptin resistance by high fat meal using the transgenic mice and ob/ob mice, because we found that the transgenic mice also became obese by the load of high fat meal. However, we found that the induction of obesity by the high fat meal load was comparable in mice with different concentrations of serum leptin. Therefore, it is the most likely that leptin is neutral in the induction of obesity by high fat meal.