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.
Perez-Tilve
Diego
D
Metabolic Diseases Institute, Division of Endocrinology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Hofmann
Susanna M
SM
Basford
Joshua
J
Nogueiras
Ruben
R
Pfluger
Paul T
PT
Patterson
James T
JT
Grant
Erin
E
Wilson-Perez
Hilary E
HE
Granholm
Norman A
NA
Arnold
Myrtha
M
Trevaskis
James L
JL
Butler
Andrew A
AA
Davidson
William S
WS
Woods
Stephen C
SC
Benoit
Stephen C
SC
Sleeman
Mark W
MW
DiMarchi
Richard D
RD
Hui
David Y
DY
Tschöp
Matthias H
MH
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