It's a vicious cycle - Obesity Sustained by Changes in Brain Biochemistry

[Reshy]

[url]http://www.sciencedaily.com/releases/2013/05/130516105511.htm[/url]

[QUOTE][B]In a new discovery reported in the Journal of Biological Chemistry, Brown University and Lifespan researchers show that in the brain cells of rats, obesity impedes the production of a hormone that curbs appetite and inspires calorie burning. The root cause appears to be a breakdown in the protein-processing mechanism of the cells. In the lab, the researchers showed they could fix the breakdown with drugs.[/B]

With obesity reaching epidemic levels in some parts of the world, scientists have only begun to understand why it is such a persistent condition. A study in the Journal of Biological Chemistry adds substantially to the story by reporting the discovery of a molecular chain of events in the brains of obese rats that undermined their ability to suppress appetite and to increase calorie burning.

A complex set of neurochemical processes, newly unraveled, shows that obesity can sustain itself, impeding hormones that would curb appetite or increase the burn rate for calories. "This is so novel. Nobody ever looked at that." Credit: David Orenstein/Brown UniversityIt's a vicious cycle, involving a breakdown in how brain cells process key proteins, that allows obesity to beget further obesity. But in a finding that might prove encouraging in the long term, the researchers at Brown University and Lifespan also found that they could intervene to break that cycle by fixing the core protein-processing problem.

Before the study, scientists knew that one mechanism in which obesity perpetuates itself was by causing resistance to leptin, a hormone that signals the brain about the status of fat in the body. But years ago senior author Eduardo A. Nillni, professor of medicine at Brown University and a researcher at Rhode Island Hospital, observed that after meals obese rats had a dearth of another key hormone -- alpha-MSH -- compared to rats of normal weight.

Alpha-MSH has two jobs in parts of the hypothalamus region of the brain. One is to suppress the activity of food-seeking brain cells. The second is to signal other brain cells to produce the hormone TRH, which prompts the thyroid gland to spur calorie burning activity in the body.

In the obese rats alpha-MSH was low, despite an abundance of leptin and despite normal levels of gene expression both for its biochemical precursor protein called pro-opiomelanocortin (POMC) and for a key enzyme called PC2 that processes POMC in brain cells. There had to be more to the story than just leptin, and it wasn't a problem with expressing the needed genes.

Nillni and his co-authors, including lead authors Isin Cakir and Nicole Cyr, conducted the new study to find out where the alpha-MSH deficit was coming from. Nillni said he suspected that the problem might lie in the brain cells' mechanism for processing the POMC protein to make alpha-MSH.[/QUOTE]

Good thing I'm skinny.