Melanocortin signaling in the CNS directly regulates circulating cholesterol
- 6 June 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 13 (7), 877-882
- https://doi.org/10.1038/nn.2569
Abstract
This study finds that inhibition of the hypothalamic melanocortin receptors increases the level of high-density lipoprotein HDL-C, a form of cholesterol, circulating in the blood stream. Uptake of HDL-C into the liver was slowed, as expression of one of the hepatic cholesterol receptors was downregulated. Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an important regulator of cholesterol in rodents. Inhibiting the brain's melanocortin system by pharmacological, genetic or endocrine mechanisms increased circulating HDL cholesterol by reducing its uptake by the liver independent of food intake or body weight. Our data suggest that a neural circuit in the brain is directly involved in the control of cholesterol metabolism by the liver.This publication has 41 references indexed in Scilit:
- Glucagon-Like Peptide 1 Stimulates Hypothalamic Proopiomelanocortin NeuronsJournal of Neuroscience, 2007
- Metabolic Syndrome: A Multiplex Cardiovascular Risk FactorJournal of Clinical Endocrinology & Metabolism, 2007
- Studies on the Physiological Functions of the Melanocortin SystemEndocrine Reviews, 2006
- Ghrelin and the short- and long-term regulation of appetite and body weightPhysiology & Behavior, 2006
- Diet-Genotype Interactions in the Development of the Obese, Insulin-Resistant Phenotype of C57BL/6J Mice Lacking Melanocortin-3 or -4 ReceptorsEndocrinology, 2006
- A brain-liver circuit regulates glucose homeostasisCell Metabolism, 2005
- The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy HomeostasisNeuron, 2003
- Prevalence of the Metabolic Syndrome Among US AdultsJAMA, 2002
- Ghrelin induces adiposity in rodentsNature, 2000
- Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesityJCI Insight, 2000