How Obesity is Linked to the Brain: Scientists Discover New Messaging System

Researchers at the University of Wisconsin-Madison, while conducting a study on mice, have discovered that a specific messaging system in the brain which directly affects the food intake and as a result, body weight.

A protein called NF-kappaB and its associated gene IKKbeta are known to be involved in metabolism in liver, fat and skeletal muscle tissues.

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When Dongsheng Cai, an assistant professor of physiology at the UW School of Medicine and Public Health, and colleagues looked for this same pathway in the hypothalamus - the part of the brain that regulates appetite and energy balance - they found it also influenced how much mice eat.

More specifically, they found overfeeding the mice spurred the pathway into action. When they suppressed the pathway's activity, the animals were significantly protected from overeating and obesity.

The researchers also examined a cell component called the endoplasmic reticulum (ER), shown recently to be involved in metabolic diseases involving over-nutrition, to see if it might play a role in linking over-nutrition to activate IKKbeta/NF-kappaB in the hypothalamus.

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"At the intracellular level, when the ER is challenged with over-nutrition, this leads to ER stress, which can push the IKKbeta/NF-kappaB pathway to an active state, although the involved reactions could be quite complicated," Cai said.

In several experiments, the researchers found that ER stress caused by over-nutrition activated IKKbeta/NF-kappaB in the hypothalamus.

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Suppressing ER stress in the central nervous system significantly preserved normal regulation of food intake and prevented obesity.

Cai said that he hopes the discovery will eventually to a better understanding of obesity, type 2 diabetes, and cardiovascular and neurodegenerative diseases - which are both fuelled by overeating.

He also hopes it will lead to new treatments and prevention strategies for those diseases.

The study is published in the Oct. 3, 2008 issue of Cell.

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