Restoring Leptin Sensitivity in the Brain
By: Felicia Breedy
Leptin, a hormone that is produced by fat cells, works through the brain to manage appetite and metabolism. Christian Bjorbaek, PhD, has published findings from his study that clarifies the mechanisms through which leptin works. He is the recipient of an award from the American Diabetes Association which is funded by the Richard and Susan Smith Family Foundation Pinnacle Project Award. Using severely obese and diabetic mice, Dr. Bjorbaek's study showed that by restoring leptin sensitivity to specific neurons in the brain (pro-opiomelanocortin or POMC), insulin levels returned to normal and activity levels increased.
Over time, many researchers have found that leptin was responsible for weight regulation and appetite control through its effects on the central nervous system. Most believed that it was through a region in the brain's hypothalamus known as the arcuate nucleus (ARC) that leptin primarily did its work. But Dr. Bjorbaek hypothesized that the POMC neurons were involved. He tested his hypothesis using obese and diabetic mice that lacked leptin receptors. He genetically restored leptin receptor activity to neurons in the POMC region. The results showed that mice not only ate fewer calories and lost weight, but their glucose levels returned to normal levels independent of food or weight changes. In addition, their activity levels increased, and actually doubled.
Dr. Bjorbaek explains the role that leptin plays, "POMC neurons may reduce the amount of glucose released into to the blood by the liver and/or increasing glucose uptake from the blood into the muscle." Another significant find is that glucose levels were restored independent of food or weight changes. These data suggest that it may be possible to normalize blood glucose without weight loss. These research findings could point to a new potential target for therapeutic drugs in the treatment of those who are obese and insulin resistant. It may even stimulate a desire to exercise in these individuals.
Dr. Bjorbaek's published findings can be found in the June 3, 2009 edition of Cell Metabolism.
(Huo L, Gamber K, Greeley S, Silva J, Huntoon N, Leng XH, Bjørbaek C. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metabolism. 2009 Jun;9(6):537-47.)
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