Expression of neuron-specific leptin receptor (LEPR) transgenes can reverse the obesity, diabetes, and infertility seen in db/db mice, which carry a defective leptin receptor, new research indicates.
As reported in the November 10th online issue of the Journal of Clinical Investigation, Dr. Streamson C. Chua, Jr., from Albert Einstein College of Medicine in New York, and colleagues created db/db mice that expressed LEPR-B transgenes.
Expression of a transgene called SYN-LEPR-B corrected obesity and the related problems to a similar extent as expression of NSE-LEPR-B, which has been reported previously. When both transgenes were expressed complete correction of the obesity, diabetes, and infertility was observed.
In mice carrying both transgenes, strong expression of the LEPR isoform was noted in energy-relevant areas of the hypothalamus. Normalized expression of three key neuropeptide genes was also seen in these animals.
The results indicate that expression of SYN-LEPR-B or NSE-LEPR-B alone cannot completely normalize energy balance in db/db mice, the authors note. Rather, expression of both transgenes is required to completely correct the metabolic disturbance.
Clin Invest online, Nov 10th 2005.
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