Reduction in the activity of the α-melanocyte-stimulating hormone (α-MSH) system causes obesity, and infusions of α-MSH can produce satiety, raising the possibility that α-MSH may mediate physiological satiety signals. Since α-MSH is coded for by the pro-opiomelanocortin (POMC) gene, we examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity characterized by leptin insufficiency (ob/ob) or leptin insensitivity (db/db). In wild-type mice, hypothalamic POMC mRNA was decreased >60% after a 2-day fast and was positively correlated with leptin mRNA. Similarly, compared with controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice. POMC mRNA was negatively correlated with both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA. Finally, treatment of both male and female ob/ob mice with leptin stimulated hypothalamic POMC mRNA by about threefold. These results suggest that impairment in production, processing, or responsiveness to α-MSH may be a common feature of obesity and that hypothalamic POMC neurons, stimulated by leptin, may constitute a link between leptin and the melanocortin system.
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February 01 1998
Hypothalamic Pro-Opiomelanocortin mRNA Is Reduced By Fasting in ob/ob and db/db Mice, but Is Stimulated by Leptin
Tooru M Mizuno;
Tooru M Mizuno
Fishberg Center for Neurobiology, Mount Sinai School of Medicine
New York, New York
Neurobiology of Aging Laboratories, and the Department of Geriatrics, Mount Sinai School of Medicine
New York, New York
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Steven P Kleopoulos;
Steven P Kleopoulos
Fishberg Center for Neurobiology, Mount Sinai School of Medicine
New York, New York
Neurobiology of Aging Laboratories, and the Department of Geriatrics, Mount Sinai School of Medicine
New York, New York
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Hugo T Bergen;
Hugo T Bergen
Department of Anatomy, University of Manitoba
Winnipeg, Manitoba, Canada
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James L Roberts;
James L Roberts
Fishberg Center for Neurobiology, Mount Sinai School of Medicine
New York, New York
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Catherine A Priest;
Catherine A Priest
Fishberg Center for Neurobiology, Mount Sinai School of Medicine
New York, New York
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Charles V Mobbs
Charles V Mobbs
Fishberg Center for Neurobiology, Mount Sinai School of Medicine
New York, New York
Neurobiology of Aging Laboratories, and the Department of Geriatrics, Mount Sinai School of Medicine
New York, New York
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Address correspondence and reprint requests to Dr. Charles V. Mobbs, Neurobiology of Aging Laboratories, Box 1639, Mt. Sinai School of Medicine, 1425 Madison Ave., New York, NY 10029-6574. E-mail: mobbsc@alum.mit.edu
Diabetes 1998;47(2):294–297
Article history
Received:
October 02 1997
Revision Received:
November 11 1997
Accepted:
November 11 1997
PubMed:
9519731
Citation
Tooru M Mizuno, Steven P Kleopoulos, Hugo T Bergen, James L Roberts, Catherine A Priest, Charles V Mobbs; Hypothalamic Pro-Opiomelanocortin mRNA Is Reduced By Fasting in ob/ob and db/db Mice, but Is Stimulated by Leptin. Diabetes 1 February 1998; 47 (2): 294–297. https://doi.org/10.2337/diab.47.2.294
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