Signals from the brain can substantially modulate cholesterol circulating in the bloodstream finds a study published online in Nature Neuroscience this week. It is important to understand how the body regulates circulating cholesterol as high levels are one of the major causes of heart attacks.
Cholesterol is crucial for animal life, but too much of it, in the form of low-density lipoprotein (LDL) complexes, can cause atherosclerosis ― thickening of the artery wall. High-density lipoprotein (HDL) cholesterol, on the other hand, can prevent atherosclerosis. How the body regulates levels of circulating LDL and HDL remains poorly understood.
Matthias Tschop and colleagues observed that increased levels of the hunger-signaling stomach hormone ghrelin not only made mice eat more and gain weight but also increased the levels of HDL cholesterol in their blood. Ghrelin is known to inhibit MC4R, a receptor in the hypothalamus that is crucial to the regulation of calorie intake and expenditure. The authors found that direct chemical blockade of MC4R also increased HDL levels. Lack of MC4R signaling caused a reduction of HDL uptake by the liver, which consequentially increased the amount of circulating HDL.
Atherosclerosis is a major health problem in industrialized countries and the cause of most heart attacks; it is therefore crucial to understand how the body regulates circulating cholesterol. However, since cholesterol metabolism in mice is quite different from that in humans, it remains to be tested whether the mechanisms uncovered in this paper also apply to people.