Tuesday, June 8, 2010

Remote control in brain for cholesterol regulation

U.S. researchers have found that circulation of cholesterol is regulated in the brain by the hunger-signaling hormone ghrelin, according to a study appearing online in Nature Neuroscience.

This finding points to a new potential target for the pharmacologic control of cholesterol levels, said researchers at the University of Cincinnati (UC).

"We have long thought that cholesterol is exclusively regulated through dietary absorption or synthesis and secretion by the liver, " said lead researcher Matthias Tschop of UC's Metabolic Diseases Institute.

"Our study shows for the first time that cholesterol is also under direct 'remote control' by specific neurocircuitry in the central nervous system."

The hormone ghrelin inhibits the melanocortin four receptor ( MC4R) in the hypothalamus and is important for the regulation of food intake and energy expenditure.

Tschop and his team found that increased levels of ghrelin in mice caused the animals to develop increased levels of blood- circulating cholesterol. This is due to a reduction in the uptake of cholesterol by the liver.

The research team next tested the effects of genetically deleting or chemically blocking MC4R in the central nervous system. This test also yielded increased levels of cholesterol, suggesting that MC4R was the central element of the "remote control."

"We were stunned to see that by switching MC4R off in the brain, we could even make injected cholesterol remain in the blood much longer," said Tschop.

Cholesterol is a type of naturally occurring fat needed by the body, but too much cholesterol can lead to atherosclerosis, a buildup of plaque in the arteries.

There are two types of cholesterol in humans-HDL (high-density lipoprotein) and LDL (low-density lipoprotein). LDL is considered the "bad" kind of cholesterol responsible for plaque buildup. HDL is the "good" kind that, in high levels, can prevent atherosclerosis.

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