Circulating cholesterol levels are maintained by balancing dietary cholesterol absorption, synthesis, and secretion by the liver and the metabolism of lipoproteins by various tissues. Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein (LDL) cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial.
Although the liver is usually regarded as the main site of cholesterol metabolism, investigators at the University of Cincinnati (Ohio, USA) have studied how cholesterol metabolism is linked to activities in the central nervous system. They reported in the June 6, 2010, online edition of the journal Nature Neuroscience that inhibiting the brain's melanocortin system by genetic engineering or with drugs increased circulating HDL cholesterol in mice by reducing its uptake by the liver independent of food intake or body weight.
They also reported that high levels of the hormone ghrelin, a natural inhibitor of the melanocortin 4 receptor (MC4R), were associated with increased circulation of HDL.
Their findings led the authors to suggest that MCR4 should be considered a promising target for future drug development.
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