Editors' ChoiceCholesterol Metabolism

Your Brain Controls Your Cholesterol

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Science Translational Medicine  16 Jun 2010:
Vol. 2, Issue 36, pp. 36ec95
DOI: 10.1126/scitranslmed.3001355

Elevated cholesterol concentrations in the blood are an established risk factor for cardiovascular disease. Worldwide, hundreds of millions of individuals take drugs like statins to reduce cholesterol or to increase proteins that transport cholesterol, such as high-density lipoprotein (HDL), which your physician likes to call the "good” cholesterol. Early on, it was thought that the cholesterol we eat is a major determinant of our circulating cholesterol levels, and many people tried to avoid eating cholesterol-rich foods like egg yolks, meat, and dairy products in order to lower their blood cholesterol. It turned out, however, that the amount of cholesterol we eat has only a modest impact on our blood cholesterol concentrations; more important, in addition to our genetic makeup, is our overall metabolic fitness. Because the brain controls metabolic functions such as hepatic glucose production and lipid metabolism in fat, it is reasonable to think that the brain might also regulate the metabolic pathways that control circulating cholesterol. Now Perez-Tilve et al. have demonstrated in a series of studies that this is the case.

These authors started off by injecting mice with the gut hormone ghrelin, which increased adiposity and cholesterol levels after one week. Because most of ghrelin’s effects on metabolism are believed to be mediated through the brain melanocortin system, they next asked whether pharmacological inhibition of the melanocortin system only in the brain would increase cholesterol concentrations—which indeed it did. This treatment altered cholesterol concentrations by decreasing the clearance of cholesterol from the circulation; thus, the brain regulates cholesterol by controlling its clearance. A second gut hormone, GLP1, which is often targeted in diabetes treatment and activates the brain melanocortin system, decreased cholesterol levels. These findings also suggest that other brain signals—nutrients, emotions, and stress, for example—could also regulate cholesterol metabolism. This may be a mechanism through which alternative medicine practices such as acupuncture and aromatherapy could regulate cardiovascular risk factors. These techniques can modulate the autonomic nervous system, which is probably the main peripheral mediator of the brain control of cholesterol metabolism.

D. Perez-Tilve, et al., Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nat. Neurosci. 6 June 2010 (10.1038/nn.2569). [Full Text]

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