Researchers at Yale School of Medicine provide direct evidence that twoparts of a neuronal system, one that promotes eating and another thatsuppresses eating, are critical for the acute regulation of eating andbody weight, according to a study published online in the September 11issue of Nature Neuroscience.
The paper makes it clear that the agouti-related peptide-expressing(AgRP) neurons are mandatory for eating. "Previous studies showed thatthe brain, particularly the hypothalamus, is responsible for theregulation of eating," said co-senior author Tamas Horvath, chair andassociate professor in the Section of Comparative Medicine, andassociate professor in neurobiology and the Department of Obstetrics,Gynecology & Reproductive Sciences. "But until now, no experimentalevidence was available to prove that AgRP neurons are critical foracute regulation of eating."
Horvath's collaborator Jens Bruening of the University of Cologne inGermany introduced the avian diphtheria toxin receptor into neurons inthe feeding support system of transgenic mice. When the animals wereadults, two injections of toxin caused the specific cell population todie within 48 hours, impairing the mouse's ability to eat and resultingin acute anorexia. These mice also showed marked reduction in bloodglucose, plasma insulin and Leptin concentrations.
"Our results confirm the hypothesis that these two systems are criticalfor eating and the cessation of eating," said Horvath. "Previoustransgenic approaches failed to provide this proof because ofcompensatory mechanisms that could operate during development. None ofthose actually knocked out neuronal function. In this case, however,neurons are gone and there is no time to replace their function."
In explaining the significance of the finding, Horvath said, "It isimportant to ensure that the multibillion dollar academic andpharmaceutical approach against metabolic disorders is leaning in theright direction. The approach in general could also eventually lead tospecific destruction of cells in other kinds of diseases."
Other authors on the study included Eva Gropp, Marya Shanabrough,Erzsebet Borak, Allison W. Xu, Ruth Janoschek, Thorsten Buch, LeonaPlum, Nina Balthasar, Brigitte Hampel, Ari Waisman, Gregory S. Barsh,and co-senior author Jens Bruning.
Citation: Nature Neuroscience, Published online September 11, in print: October 2005 Vol. 8 No. 10
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