Mind over mass: Cholesterol levels might be controlled by brain circuitry

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When your stomach growls and you have the urge to reach for the nearest snack, it is, in a way, your tummy talking. Those signals are in part sparked by the gut-based hunger hormone ghrelin, which blocks certain receptors in the brain, telling your body when it is time to eat.

But a team of researchers thinks this hormone might be doing more than just urging you to pile on some calories. It might also be helping to regulate the levels of cholesterol in your bloodstream. The new research was published online June 6 in Nature Neuroscience (Scientific American is part of Nature Publishing Group).


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Although so-called bad cholesterol (low-density lipoprotein, or LDL) can result in clogged arteries and cardiovascular disease, good cholesterol (high-density lipoprotein, or HDL) is thought to actually prevent plaque build-up in the arteries by helping to transport lipids more smoothly through the bloodstream. Cholesterol levels have long been thought to be mainly a factor of diet and liver function. But new research in mouse models shows that changes in ghrelin and in a ghrelin-inhibited receptor in the hypothalamus altered how much HDL went to the liver for processing and how much remained in the blood stream.

"Our study shows for the first time that cholesterol is also under direct 'remote control' by specific neurocircuitry in the central nervous system," Matthias Tschöp, a professor of endocrinology at the University of Cincinnati and coauthor of the paper, said in a prepared statement.

More specifically, by upping the levels of ghrelin in the mice, the researchers saw an increased amount of HDL cholesterol in the bloodstreams of the lab animals—regardless of diet or body mass. Because higher levels of HDL are thought to help prevent build-up of arterial plaque, boosting levels of it in the bloodstream could be a good way to fight harmfully high levels of LDL. The researchers got the same high HDL levels results when they blocked the hypothalamus' melanocortin 4 receptor (MC4R) either by knocking it out or shutting it down with other chemicals.

"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," Tschöp noted. Although further research will be necessary to see if the same pathway is active in humans, the link could pave the way for drugs that treat cholesterol or metabolic syndrome by targeting this hormone or brain receptor.

Image courtesy of iStockphoto/theasis

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