Melanocortin signaling in the CNS directly regulates circulating cholesterol

Diego Perez-Tilve; Susanna M. Hofmann; Joshua Basford; Ruben Nogueiras; Paul T. Pfluger; James T. Patterson; Erin Grant; Hilary E. Wilson-Perez; Norman A. Granholm; Myrtha Arnold; James L. Trevaskis; Andrew A. Butler; William S. Davidson; Stephen C. Woods; Stephen C. Benoit; Mark W. Sleeman; Richard D. Dimarchi; David Y. Hui; Matthias H. Tschöp

doi:10.1038/nn.2569

Melanocortin signaling in the CNS directly regulates circulating cholesterol

Diego Perez-Tilve, Susanna M. Hofmann, Joshua Basford, Ruben Nogueiras, Paul T. Pfluger, James T. Patterson, Erin Grant, Hilary E. Wilson-Perez, Norman A. Granholm, Myrtha Arnold, James L. Trevaskis, Andrew A. Butler, William S. Davidson, Stephen C. Woods, Stephen C. Benoit, Mark W. Sleeman, Richard D. Dimarchi, David Y. Hui, Matthias H. Tschöp

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	877-882
Number of pages	6
Journal	Nature Neuroscience
Volume	13
Issue number	7
DOIs	https://doi.org/10.1038/nn.2569
State	Published - Jul 2010
Externally published	Yes

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Perez-Tilve, D., Hofmann, S. M., Basford, J., Nogueiras, R., Pfluger, P. T., Patterson, J. T., Grant, E., Wilson-Perez, H. E., Granholm, N. A., Arnold, M., Trevaskis, J. L., Butler, A. A., Davidson, W. S., Woods, S. C., Benoit, S. C., Sleeman, M. W., Dimarchi, R. D., Hui, D. Y., & Tschöp, M. H. (2010). Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nature Neuroscience, 13(7), 877-882. https://doi.org/10.1038/nn.2569

@article{1df6521bd46a49c19663685bc99a7c4c,

title = "Melanocortin signaling in the CNS directly regulates circulating cholesterol",

abstract = "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.",

author = "Diego Perez-Tilve and Hofmann, {Susanna M.} and Joshua Basford and Ruben Nogueiras and Pfluger, {Paul T.} and Patterson, {James T.} and Erin Grant and Wilson-Perez, {Hilary E.} and Granholm, {Norman A.} and Myrtha Arnold and Trevaskis, {James L.} and Butler, {Andrew A.} and Davidson, {William S.} and Woods, {Stephen C.} and Benoit, {Stephen C.} and Sleeman, {Mark W.} and Dimarchi, {Richard D.} and Hui, {David Y.} and Tsch{\"o}p, {Matthias H.}",

note = "Funding Information: This work was supported by US National Institute of Health grants NIDDK56863 (S.C.W. and M.H.T.), 5R01DK077975 (M.H.T.), R01 DK076907 (D.Y.H.) and HL67093 (W.S.D.). S.M.H. is the recipient of a Scientist Development Award from the American Heart Association (#0635079N). S.M.H. is a recipient of a Basic Science Award (110BS72) from the American Diabetes Association.",

year = "2010",

month = jul,

doi = "10.1038/nn.2569",

language = "English",

volume = "13",

pages = "877--882",

journal = "Nature Neuroscience",

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Perez-Tilve, D, Hofmann, SM, Basford, J, Nogueiras, R, Pfluger, PT, Patterson, JT, Grant, E, Wilson-Perez, HE, Granholm, NA, Arnold, M, Trevaskis, JL, Butler, AA, Davidson, WS, Woods, SC, Benoit, SC, Sleeman, MW, Dimarchi, RD, Hui, DY & Tschöp, MH 2010, 'Melanocortin signaling in the CNS directly regulates circulating cholesterol', Nature Neuroscience, vol. 13, no. 7, pp. 877-882. https://doi.org/10.1038/nn.2569

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AU - Perez-Tilve, Diego

AU - Hofmann, Susanna M.

AU - Basford, Joshua

AU - Nogueiras, Ruben

AU - Pfluger, Paul T.

AU - Patterson, James T.

AU - Grant, Erin

AU - Wilson-Perez, Hilary E.

AU - Granholm, Norman A.

AU - Arnold, Myrtha

AU - Trevaskis, James L.

AU - Butler, Andrew A.

AU - Davidson, William S.

AU - Woods, Stephen C.

AU - Benoit, Stephen C.

AU - Sleeman, Mark W.

AU - Dimarchi, Richard D.

AU - Hui, David Y.

AU - Tschöp, Matthias H.

N1 - Funding Information: This work was supported by US National Institute of Health grants NIDDK56863 (S.C.W. and M.H.T.), 5R01DK077975 (M.H.T.), R01 DK076907 (D.Y.H.) and HL67093 (W.S.D.). S.M.H. is the recipient of a Scientist Development Award from the American Heart Association (#0635079N). S.M.H. is a recipient of a Basic Science Award (110BS72) from the American Diabetes Association.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

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DO - 10.1038/nn.2569

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VL - 13

SP - 877

EP - 882

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 7

ER -

Melanocortin signaling in the CNS directly regulates circulating cholesterol

Abstract

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