Calorie overload sends the brain haywire: study

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Calorie overload sends the brain haywire: study

By Maggie Fox, Health and Science EditorThu Oct 2, 3:05 PM ET

Overeating makes the brain go haywire, prompting a cascade of damage

that may cause diabetes, heart disease and other ills, U.S.

researchers reported on Thursday.

Eating too much appears to activate a usually dormant immune system

pathway in the brain, sending out immune cells to attack and destroy

invaders that are not there, Dongsheng Cai of the University of

Wisconsin-Madison and colleagues found.

The finding, reported in the journal Cell, could help explain why

obesity causes so many different diseases. It might also offer a way

to prevent obesity itself.

" This pathway is usually present but inactive in the brain, " Cai said

in a statement.

Obesity is a growing global problem, with 1.8 billion people estimated

to be overweight or obese in 2007. Drugs marketed so far to fight

obesity have only limited success and, often, severe side-effects.

Cai's team worked in mice, seeking to explain studies that have shown

that obesity causes chronic inflammation throughout the body. This

inflammation is found in a range of diseases related to obesity,

including heart disease and diabetes.

They homed in on a compound known as IKKbeta/NK-kappaB.

Immune cells such as macrophages and leukocytes use it but Cai's team

found it in the hypothalamus, a part of the brain linked with

metabolism in mice and humans alike.

" The hypothalamus is the 'headquarters' for regulating energy, " they

wrote.

They found high levels of the compound there but it was normally inactive.

When they fed mice a high-fat diet, it became extremely active. And

when it was active, the body ignored signals from leptin, a hormone

that normally helps regulate appetite, and insulin, which helps

convert food into energy.

Stimulating IKKbeta/NK-kappaB made the mice eat more, while

suppressing it made them eat less.

Cai believes his team has discovered a master switch for the diseases

caused by overeating.

" Hypothalamic IKKb/NF-kB could underlie the entire family of modern

diseases induced by overnutrition and obesity, " his team wrote.

Cai does not know why this compound would be in the brain and in the

immune system but suspects it evolved long ago in primitive animals

that do not have the same sophisticated immune system as modern

animals, including mice and humans.

" Presumably it played some role to guide the immune defense, " Cai said

in a telephone interview. " In today's society, this pathway is

mobilized by a different environmental challenge -- overnutrition. "

" Knocking out " the gene using genetic engineering kept mice eating

normally and prevented obesity. This cannot be done in people but Cai

believes a drug, or even gene therapy, might work.

With gene therapy, a virus or other so-called vector is used to carry

corrective DNA into the body, but the approach is still highly

experimental.

(Editing by Steenhuysen and O'Callaghan)