Cellular problems found behind complex obesity syndrome

besity may be common in people with the disorder, including improperly controlled or targeted neurons, improper hormone release, and improper growth of fat cells, all of which may short-circuit normal appetite controls. However, experiments with genetically engineered mice will be necessary to know for sure, he says.

Although the work is far from revealing an anti-obesity "magic bullet," the researchers, also from Simon Fraser University in Canada and the University College London, say it does point to microtubule failure as a primary mechanism for the problems seen in BBS, particularly the disorder's obesity, diabetes and retinal degeneration. Moreover, their discovery adds to evidence that the cells' highway system could be a major factor in other multisystem disorders.

"It's becoming very clear that microtubules are so fundamental to cells that if you hit the system with a genetic mutation you will get a disease," says Katsanis. "It's likely that some genes implicated in other multisystem disorders may compromise microtubules' functions, especially in diseases whose physical characteristics overlap with those of BBS."

Microtubules act as the roads that chromosomes travel in order to move to opposite sides of the cell during cell division. They also transport molecules and packets of molecules to the cell membrane for release from the cell, and are the primary skeleton in cellular structures called cilia. BBS4 mutations are likely to affect different microtubule functions in different cell types, including the transport of proteins up and down cilia, Katsanis says.

"In our in vitro systems, if BBS4 didn't work, all the cells died because of microtubule failure," says Katsanis. "It's very likely that in engineered mice, we also may see slower growth, less cell division, and other mutation-induced changes that will explain the condition's various effects. Cell death won't be the only problem."


Contact: Joanna Downer
Johns Hopkins Medical Institutions

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