Melanocortin signaling in the CNS directly regulates circulating cholesterol.
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.
Metabolic Diseases Institute, Division of Endocrinology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Diego
D
Perez-Tilve
Susanna M
SM
Hofmann
Joshua
J
Basford
Ruben
R
Nogueiras
Paul T
PT
Pfluger
James T
JT
Patterson
Erin
E
Grant
Hilary E
HE
Wilson-Perez
Norman A
NA
Granholm
Myrtha
M
Arnold
James L
JL
Trevaskis
Andrew A
AA
Butler
William S
WS
Davidson
Stephen C
SC
Woods
Stephen C
SC
Benoit
Mark W
MW
Sleeman
Richard D
RD
DiMarchi
David Y
DY
Hui
Matthias H
MH
Tschöp
D000818:Animals; D001835:Body Weight; D018955:CD36 Antigens / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004435:Eating; D054439:Ghrelin / Q000235:genetics / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D053486:Melanocortins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044101:Receptors, Melanocortin / Q000235:genetics / Q000502:physiology; D051122:Scavenger Receptors, Class B / Q000378:metabolism
D018955:CD36 Antigens; D008076:Cholesterol, HDL; D054439:Ghrelin; D053486:Melanocortins; D044101:Receptors, Melanocortin; D051122:Scavenger Receptors, Class B; D052216:Glucagon-Like Peptide 1