This month in Nature Neuroscience an article was published by the University of Cincinnati College of Medicine (Perez-Tilve et al.) detailing the effects of the neuroendocrine system on cholesterol levels. According to the article, hypercholesterolemia (high cholesterol) is difficult to treat as a whole because there isn’t much known about the molecular origin of the condition. Unfortunately, symptoms are too well known: obesity, high blood pressure, poor glucose metabolism. The research presented shows a link between high levels of the hormone ghrelin and high cholesterol.
In one portion of the study, mice given ghrelin for a week showed increases in body fat and in cholesterol, but control mice did not. Ghrelin, which makes you feel hungry, acts on a central nervous system circuit called the central melanocortin system. When mice were given melanocortin inhibitors, HDL cholesterol increased, implying that melanocortin receptors regulate HDL regardless of food eaten.
Another hormone, GLP-1, was tested in the mice. This hormone makes you feel satisfied after having eaten, so the researchers gave mice infusions of GLP-1 for a week. Their cholesterol decreased compared with the control mice – so it was concluded that gastrointestinal hormones can regulate cholesterol both positively and negatively. Additional research showed that mice that were deficient in the genes that code for GLP-1 receptors had higher cholesterol than wild-type mice.
Perhaps in the near future the use of statins to control cholesterol levels could be decreased or even eliminated. While the cardiovascular implications of high cholesterol are dangerous, so are the side-effects of the treatment. Statins, the common treatment for high cholesterol, don’t deal with the regulatory hormones; instead, they inhibit enzymes that take part in the synthesis of cholesterol. They also don’t work to reduce triglyceride levels and raise HDL levels. Although HDL is known as “good cholesterol” the study showed that rats with high HDL were susceptible to atherosclerosis and symptoms of high cholesterol. Pharmaceutical research is already being directed toward finding agonists for GLP-1 receptors and antagonists for ghrelin receptors in order to treat all of the symptoms of hypercholesterolemia.