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Leptin, Neuronal Connections and Appetite Control, Part II


Researchers generated normal and leptin-production deficient mice called ob/ob, which contained fluorescently marked neurons. Then, they compared neurons in both breeds. One of the main co-authors of the article —Aaron G. Roseberry from Friedman’s lab—compared the electrophysiological characteristics of both types of neurons in a normal mice and in ob/ob. These studies discovered the relative activity of both types of neurons in the two mouse breeds.

Another co-author —Shirly Pinto from Friedman’s lab—worked with Horvath to do microscopy comparative research of the marked neurons in both breeds of mice. This research showed the relative number of stimulation and inhibition neuronal connections in both types of mice. Both research groups revealed that leptin acted directly to reorganize the nerve connection patterns of the neuronal nourishment circuit in the mice’s brains, particularly suppressing NPY neurons and stimulating POMC neurons. Researchers also discovered that leptin administration to ob/ob mice; deficient in leptin, produced alterations in neuronal connections—and in their electrical activity—to imitate the connections of the normal mice. The neuronal alterations preceded the behavioral changes in ob/ob mice. This is important, according to Friedman, because it suggests a relationship of cause-effect between the reorganization of nerve connection patterns and the feeding behavior.

Additionally, when researchers tested the effects of ghrelin (another peptide that stimulates appetite) over the two types of neurons in the normal animals, also noticed a decrease in the stimulation connections with POMC neurons. “Together, the results with leptin and ghrelin suggest that the findings of this reorganization of nerve connection patterns are general”, said Friedman.

“In general, these results start to suggest that the pattern diagram of the nourishment circuit nerve connections is highly dynamic”, said Friedman. “And at least they make us ask ourselves in what degree the nerve connections pattern diagram of these nerve circuits is different between obese people and slim people”.

“If we knew that the basic circuit that controls nourishment has different nerve connection patterns in different people, this could change the public perception over the causes of obesity”, said Friedman. “Some people could have a more potent impulse to eat and to weight more than others. And it could mean that conscious factors could not completely explain the way in which a person eats”.

With time, such results could also contribute to a wider understanding of why leptin administration could reduce weight in some people and obese animals, but not in others. The variable response to leptin suggests that some individuals are obese because they are resistant to leptin. Advances on the way leptin functions in the brain could lead to a better understanding of leptin resistance and obesity and could finally lead to new ways of fighting obesity.


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